Hybrid-Capture Sequencing for Determining Immune Cell Clonality

ABSTRACT

In an aspect, there is provided, a method of capturing a population of T-Cell receptor and/or immunoglobulin sequences with variable regions within a patient sample, said method comprising: extracting/preparing DNA fragments from the patient sample; ligating a nucleic acid adapter to the DNA fragments, the nucleic acid adapter suitable for recognition by a pre-selected nucleic acid probe; capturing DNA fragments existing in the patient sample using a collection of nucleic acid hybrid capture probes, wherein each capture probe is designed to hybridize to a known V gene segment and/or a J gene segment within the T cell receptor and/or immunoglobulin genomic loci.

FIELD OF THE INVENTION

The invention relates to methods of capturing and sequencing immune-associated nucleotide sequences, and more particularly to methods of determining clonality of immune cells.

BACKGROUND OF THE INVENTION

The maturation of lymphocytes is a fascinating process that is marked not only by immunophenotypic changes, but also by discrete and regulated molecular events⁽¹⁻³⁾. As T-cells mature, an important part of the associated molecular “maturation” involves the somatic alteration of the germline configuration of the T-cell receptor (TR) genes to a semi-unique configuration in order to permit the development of a clone of T-cells with an extracellular receptor specific to a given antigen⁽¹⁻³⁾. B-cells undergo a similar maturation process involving different loci that encode the antibody-containing B-cell receptor (BC). These clones, when considered together as a population, produce a repertoire of antigen sensitivity orders of magnitude larger than would be possible by way of inherited immunological diversity alone⁽³⁾. Indeed, the somatic rearrangement of the TR and BR genes is one of the key ontological events permitting the adaptive immune response⁽³⁾.

When molecular carcinogenesis occurs in a lymphoid cell lineage, the result is the selective growth and expansion of the tumoural lymphocytes relative to their normal counterparts⁽²⁾. The so-called precursor (historically termed “lymphoblastic”) lesions are believed to reflect molecular carcinogenesis in lymphoid cells at a relatively immature stage of maturation⁽²⁾. In contrast, if molecular carcinogenesis occurs at a point during or after the process of T-cell receptor gene re-arrangement (TRGR), the result is a “mature” (often also termed “peripheral”) T-cell lymphoma in which the tumour contains a massively expanded population of malignant T-cells with an immunophenotype reminiscent of mature lymphocytes, most if not all bearing an identical TR gene configuration⁽⁴⁾. It is this molecular “homogeneity” of the TR configuration within a T-cell neoplasm that defines the concept of clonality in T-cell neoplasia^((1,2,4)).

The T-cell receptor is a heteroduplex molecule anchored to the external surface of T lymphocytes^((5,21)); there the TR, in cooperation with numerous additional signalling and structural proteins, functions to recognize an antigen with a high degree of specificity. This specificity, and indeed the vast array of potential antigenic epitopes that may be recognized by the population of T-cells on the whole, is afforded by (1) the number of TR encoding regions of a given T-cell receptor's genes as present in the germline; and (2) the intrinsic capacity of the TR gene loci to undergo somatic re-arrangement⁽³⁾. There are four TR gene loci, whose protein products combine selectively to form functional TRs: T-cell receptor alpha (TRA) and T-cell receptor beta (TRB) encode the α and β chains, respectively, whose protein products pair to form a functional α/β TR; T-cell receptor gamma (TRG) and T-cell receptor delta (TRD) encode the γ and δ chains, respectively, whose protein products pair to form a functional γ/δ TR. The vast majority (>95%) of circulating T-cells are of the α/β type^((21,22)); for reasons as yet not fully understood, γ/δ T-cells tend to home mainly to epithelial tissues (e.g. skin and mucosae) and appear to have a different function than the more common α/β type T-cells.

The TRA locus is found on the long arm of chromosome 14 in band 14q11.2 and spans a total of 1000 kilobases (kb)⁽²³⁾; interestingly, sandwiched between the TRA V and J domains, is the TRD locus (14q11.2), itself spanning only 60 kb⁽²⁴⁾. The TRB locus is found on the long arm of chromosome 7 in band 7q35 and spans a total of 620 kb⁽²⁵⁾. The TRG locus is found on the short arm of chromosome 7 in region 7p15-p14 and spans 160 kb⁽²⁶⁾.

Within each TR gene locus are a variable number of variable (V) and join (J) segments⁽²³⁻²⁶⁾; additional diversity (D) segments are present within the TRB and TRD loci^((24,25)). These V, D and J segments are grouped into respective V, D and J regions (see FIG. 1-1). In the germline configuration, a full complement of V (numbering from 4-6 in TRG to 45-47 in TRA), D (2 in TRB and 3 in TRD) and J (numbering as few as 4 in TRD to as many as 61 in TRA) segments can be detected, varying based on inheritance⁽²³⁻²⁶⁾. In this configuration, the specificity of any resulting coding sequence would be uniformly based on inherited variation. During maturation, however, somatic mutation (i.e. rearrangement) occurs such that there is semi-random recombination of variable numbers of the V, D and J segments to produce a lineage of cells with a “re-arranged” configuration of TR gene segments. This gene re-arrangement, when later subject to gene transcription and translation, produces a TR unique to the given T-lymphocyte (and its potential daughter cells). This process is represented pictorially in FIG. 1-2. Although the specific details of this re-arrangement process are far beyond the scope of this work, the process is at least partly mediated by enzymes of similar function to those used to perform splicing^((21,22)).

BIOMED-2⁽²⁹⁾ is a product of several years of collaborative expert study, resulting in a thoroughly studied consensus T-cell clonality assay. The BIOMED-2 assay includes multiplexed primer sets for both Immunoglobulin (IG) and TR clonality assessment and can be implemented with commercially available electrophoresis systems (e.g. Applied Biosystems fluorescence electrophoresis platforms)⁽²⁹⁾. These commercially available primer sets have the advantage of standardization and ease of implementation. In addition, by virtue of the extensive study performed by the BIOMED consortium, the BIOMED-2 assay has the well-documented advantage of capturing the mono-clonality of the vast majority of control lymphomas bearing productive T-cell receptors (i.e. flow-sorted positive for either α/β or γ/δ T-cell receptors) using the specified TRB and TRG primer sets⁽²⁹⁾. Of note, having been in use for over a decade, the BIOMED-2 has been globally accepted as the diagnostic assay primer set of choice.

The current approach to TRGR testing is subject to a number of technical and practical caveats that dilute the applicability of TRGR testing to the full breadth of real-world contexts.

Because the PCR-based techniques that are employed in TRGR assays are subject to amplicon size restrictions^((29,34)) the sheer size of the TRA locus prevents a complete assay of the TRA gene in clinical settings. Indeed, although of smaller size, the TRB locus as a whole is also prohibitively large to sequence in its germline configuration. It is therefore of no surprise that much of the published data pertaining to the utility and validity of TRGR assays has stemmed from assays specific to only subparts of TRB as well as TRG, a locus of size much more amenable to a single-assay. In addition, since the TRD locus is often deleted after TR gene rearrangement (since it is contained within the TRA locus and excised whenever the TRA locus is rearranged), assays for TRD have also not been as rigorously studied. For this reason, any BIOMED-2-based T-cell clonality assay aimed at directing immunotherapy, requiring a complete sequence-based understanding of the TR genes involved, would be insufficient.

The BIOMED-2 assay is subject to additional technical challenges. As part of the standard TRGR assay, most laboratories rely on the demonstration of electrophoretic migration patterns for the determination of TR clonality. Interpretation of the assay depends on the demonstration (or lack thereof) of a dominant amplicon of specific (albeit not pre-defined) molecular weight, rather than the normal Gaussian distribution of amplicons of variable size. This approach, as has been described previously⁽³⁵⁻³⁷⁾, is subject to interpretative error and other technical problems. Also, given the large amounts of DNA required for the multitude of multiplex tubes making up the assay, the overall assay can very quickly deplete DNA supplies, especially when obtained from limited sample sources.

Finally, and arguably of greatest import, is the issue of diagnostic bias used in the study of TRGR assay performance. More precisely, when laboratories seek to validate a TRGR assay, the requirement of “standard” samples will typically require that the laboratory utilize previously established clonal samples or samples previously diagnosed and accepted to represent clonal entities (e.g. previously diagnosed cases of lymphoma); these samples are in turn compared to “normal” controls. In contrast, the demographics of subsequent “real-life” test samples are unlikely to be so decidedly parsed into “normal” and “abnormal” subsets.

Current T-Cell Receptor (TCR) rearrangement profiling assays rely on targeted PCR amplification of rearranged TCR genomic loci. The simplest method for assessing clonality of T-cells involves qualitative assessment through multiplexed amplification of the individual loci using defined primer sets and interpretation of fragment size distributions according to the BIOMED2 protocol^(A1,2). Next-generation sequencing can be used as a read-out to provide quantitative assessment of the TCR repertoire including detection of low abundance rearrangements from bulk immune cells, or even pairing of the heterodimeric chain sequences with single cell preparation methods^(A3,4). Hybrid-capture based library subsetting is an alternative method to PCR-based amplification that can improve coverage uniformity and library complexity when sample is not limiting and allows for targeted enrichment of genetic loci of interest from individual genes to entire exomes^(A5). In hybrid-capture methods, the formation of probe-library fragment DNA duplexes are used to recover regions of interest^(A6 7,8).

Similar to T-cells, B-cells involved in adaptive immunity also undergo somatic rearrangement of germline DNA to encode a functional B-cell receptor (BR). Like TRs, these sequences comprise by discrete V, D, J segments that are rearranged and potentially altered during B-cell maturation to encode a diversity of unique immunoglobulin proteins. The clonal diversity of B-cell populations may have clinical utility and, similar to T-cell lymphomas, several cancers are characterized by clonal expansion of specific BR/Ig sequences.

SUMMARY OF THE INVENTION

There is described herein, the development of a novel NGS-based T-cell clonality assay, incorporating all four TR loci. The assay was both analytically and clinically validated. For the former, a series of idealized specimens was used, with combined PCR/Electrophoresis and Sanger Sequencing to confirm NGS-data. The latter validation compared NGS results to the current gold standard for clinical T-cell clonality testing (i.e. the BIOMED-2 primer PCR method) on an appropriately-sized minimally-biased sample of hematopathology specimens. In the latter dataset also, the patterns of T-cell clonality were also correlated with clinical, pathologic, and outcome data.

In an aspect, there is provided, a method of capturing a population of T-Cell receptor and/or immunoglobulin sequences with variable regions within a patient sample, said method comprising: extracting/preparing DNA fragments from the patient sample; ligating a nucleic acid adapter to the DNA fragments, the nucleic acid adapter suitable for recognition by a pre-selected nucleic acid probe; capturing DNA fragments existing in the patient sample using a collection of nucleic acid hybrid capture probes, wherein each capture probe is designed to hybridize to a known V gene segment and/or a J gene segment within the T cell receptor and/or immunoglobulin genomic loci.

In an aspect, there is provided, a method of immunologically classifying a population of T-Cell receptor and/or immunoglobulin sequences, the method comprising:

(a) identifying all sequences containing a V gene segment from the sequences of the DNA fragments by aligning the sequences of the DNA fragments to a library of known V gene segment sequences;

(b) trimming the identified sequences in (a) to remove any sequences corresponding to V gene segments to produce a collection of V-trimmed nucleotide sequences;

(c) identifying all sequences containing a J gene segment in the population of V-trimmed nucleotide sequences by aligning the V-trimmed nucleotide sequences to a library of known J gene segment sequences;

(d) trimming the V-trimmed nucleotide sequences identified in (c) to remove any sequences corresponding to J gene segments to produce VJ-trimmed nucleotide sequences;

(e) identifying any D gene segment comprised in the VJ-trimmed nucleotide sequences identified in (d) by aligning the VJ-trimmed nucleotide sequences to a library of known D gene segment sequences;

(f) for each VJ-trimmed nucleotides sequence identified in (d), assembling a nucleotide sequence comprising the V gene segment, any D gene segment, and the J gene segment identified in steps (a), (e) and (c) respectively;

(g) selecting from the nucleotide sequence assembled in step (f) a junction nucleotide sequence comprising at least the junction between the V gene segment and the J gene segment, including any D gene segment, the junction nucleotide sequence comprising between 18 bp and 140 bp, preferably 40-100 bp, further preferably about 80 bp;

and optionally (h) and (i):

(h) translating each reading frame of the junction nucleotide sequence and its complementary strand to produce 6 translated sequences; and

(i) comparing the 6 translated sequences to a library of known CDR3 regions of T-Cell receptor and/or immunoglobulin sequences to identify the CDR3 region in the DNA fragments.

In an aspect, there is provided, a method of identifying CDR3 regions in T-Cell receptor and/or immunoglobulin sequences, the method comprising:

(a) identifying a V gene segment comprised in the immunoglobulin sequence by aligning the immunoglobulin sequence to a library of known V gene segment sequences;

(b) identifying a J gene segment comprised in the immunoglobulin sequence by aligning the immunoglobulin sequence to a library of known J gene segment sequences;

(c) if V and J gene segments are identified, then comparing the immunoglobulin sequence to a library of known CDR3 regions of T-Cell receptor and/or immunoglobulin sequences to identify any CDR3 region in the immunoglobulin sequence.

BRIEF DESCRIPTION OF FIGURES

These and other features of the preferred embodiments of the invention will become more apparent in the following detailed description in which reference is made to the appended drawings wherein:

FIG. 1-1: Genomic distribution of the TRA, TRB, TRD and TRG locus genes. The inner ring highlights the relevant portions of chromosome 7 (blue) and chromosome 14 (red); the relative positions of each of the genes is denoted in the ideogram, indexed by chromosome position (bp×1000), with the accompanying HUGO accepted gene symbols.

FIG. 1-2: TRGR Situated Relative to Controlled & Uncontrolled (Malignant) T-cell Expansion. The path of maturation from Pre T-cell to mature T-cell is outlined, including the TR gene rearrangement; additionally, accumulated mutations might then lead to the uncontrolled cell growth, characteristic of mature T-cell lymphoma.

FIG. 2-1A: TRGR Assay Wet-Bench Work-Flow Schematic. 1, DNA isolation; 2, Shearing (˜200 bp); 3, Library Production; 4, Hybridization with Biotinylated DNA Probes; 5, Enrichment with Streptavidin-Bound Paramagnetic Beads; 6, PCR; 7, Illumina sequencing.

FIG. 2-1B: TRGR Assay Informatic Work-Flow Schematic. 1, Paired-end 150 bp DNA sequencing is performed; 2, Merging of paired ends (e.g. PEAR pipeline); 3, TRSeq pipeline (outputs may include Clonotype table, Coverage histograms and Circos plots).

FIG. 2-2: Schematic Representation of V and J Gene Probe Placement Relative to the Germline. The germline V-genes are highlighted in solid red, with 100 bp probe placement shown above; probes are oriented inward and abut the 5′ & 3′ ends of the germline V-gene configuration. The germline J-genes are highlighted in solid blue, with 100 bp probe placement shown above; J-gene probes cover the entire J-gene, and on occasion some flanking extragenic sequence.

FIG. 3-1A: Read Length Simulation Results. In this simulation, the percent of total BWA-detectable VDJ gene combinations obtained by reference sequence concatenation was computed. Note that a plateau of maximal sensitivity could be inferred with a read length of approximately 200 bp or more.

FIG. 3-1B: TRBV6 Group Phylogenetic Sequence Alignment. A post-hoc analysis of the TRBV6 group by phylogenetic comparison of reference sequences suggested that the TRBV6-2 01-allele and TRBV6-3 gene are more closely related than the TRBV6-2 01 & 02 alleles, a seeming violation of the IMGT naming/numbering system.

FIG. 3-1C: TRGJ Group Phylogenetic Sequence Alignment. A post-hoc analysis of the TRGJ group by phylogenetic comparison of reference sequences suggested that the TRGJ1 02-allele and TRGJ2 gene are more closely related than the TRGJ1 01 & 02-alleles, a seeming violation of the IMGT naming/numbering system.

FIG. 3-2: Empirical determination of MATLAB alignment score cut-off values.

FIG. 3-3: First Run TapeStation tracings Pre-Library (post-shearing) vs. Post-Library Preparation. In this tableau, each specimen's electropherogram tracing before & after library preparation is displayed (one above the other) in order to compare the library preparation adapter/barcode ligation success & expected increase in average fragment length of approximately 100 bp. Part 1: Specimens A037, L2D8, OV7 & CEM. Part 2: Specimens EZM, Jurkat, TIL2, MOLT4, STIM1, SUPT1.

FIG. 3-4: PEAR Algorithm Read-Merge & Assembly Results for each first-run specimen.

FIG. 3-5: First Run Comparison of PEAR-produced input Reads (blue) vs. Reads-on-Target (yellow).

FIG. 3-6: First Run Summary Coverage Statistics. Mean Depth of Coverage and Percent of Genes with Greater than 100× Coverage shown.

FIG. 3-7A: Histogram of V-J gene alignment pair counts for sample A037. Healthy patient peripheral blood specimen demonstrating a “polyclonal” process, for comparison with a clonal specimen delineated in FIG. 3-7B.

FIG. 3-7B: Histogram of V-J gene alignment pair counts for a selected clonal specimen. CEM cell line demonstrating a “clonal” process, for comparison with the polyclonal specimen of FIG. 3-7A. FIG. 3-8A: First Run Lymphocyte Sample Circos Plots. The ideogram represents all intra-locus V-J combinations (color coded by locus: TRA red; TRB blue; TRD yellow; TRG green); the height and width of the gray bars are determined by read counts of identical V & J gene name and CDR3 sequence triads.

FIG. 3-8B: First Run Cell Line Circos Plots. The ideogram represents all intra-locus V-J combinations (color coded by locus: TRA red; TRB blue; TRD yellow; TRG green); the height and width of the gray bars are determined by read counts of identical V & J gene name and CDR3 sequence triads.

FIG. 3-8C: Tableaus of coverage histograms for V and J genes across all four TR loci for each of the six lymphocyte samples. Specimens more characteristically “polyclonal” show a uniform coverage across most if not all genes, at greater than 100×; specimens more seemingly “clonal” tend to show at least a subset of genes at coverage less than 100×.

FIG. 3-8D: Tableau of coverage histograms for V and J genes across all four TR loci for each of the four cell line samples. These clonal specimens uniformly show at least a subset of genes at coverage less than 100×.

FIG. 3-9: First Run TRSeq algorithm performance metrics relative to the IMGT/High V-Quest Pipeline. This boxplot highlights the percent concordance of calls made by the TRSeq pipeline across all four loci and over all 10 specimens for each of overall read rearrangement status, and named V, D, and J-gene concordance relative to the calls made by the IMGT/High V-Quest system.

FIG. 3-10: Analytical Validation PCR/Electrophoresis Design. The experiment was performed in a 384-well plate with samples listed by column and primer combinations (V-gene forward & J-gene reverse complement) listed by row; W=water; E=empty; ▪=reaction selected for PCR purification & Sanger Sequencing; ***=excluded from subsequent analyses due to primer sequence redundancy (see methods/results).

FIG. 3-11: Analytical Validation Electrophoresis Composite Gel Photographs. Gels are listed by Specimen Name. Primer Combinations (V-gene forward & J-gene reverse complement) are listed along the x-axes; 100 bp ladders are shown along the y-axes. Interpretation of the banding patterns, by expected amplicon size and by intensity, is outlined in Table 3.1A.

FIG. 3-12A: ROC Plot by Strong PCR/Electrophoresis Band. ROC Curve Cut-offs vary by normalized read count shown.

FIG. 3-12B: ROC Plot, Any PCR/Electrophoresis Band of Reasonable Molecular Weight. ROC Curve Cut-offs vary by normalized read count shown.

FIG. 3-13: Analytical Validation Sanger Sequencing Results. In this analysis, the CDR3 sequence from each TRGR configuration is aligned to the corrected Sanger Sequence (with the number of reads of each configuration also tallied); the diagrams below delineate this alignment process for each of the PCR reactions submitted for Sanger Sequencing, as highlighted in FIG. 3-10, excluding those cases rejected due to false-positive amplification using the TRGJ2 primer and cases not containing TRSeq-identifiable CDR3 sequences (for a total of 32 of 47 reactions).

FIG. 3-14: Sanger Sequencing Receiver-Operating Characteristic Curve. Using a k-mer-based analysis, the TRSeq-generated CDR3 sequences were compared to the Sanger Sequence results. For each applicable primer configuration, the corresponding TRSeq-generated CDR3 sequence was aligned using PHRED-based quality-score adjustment as a k-mer across the length of the Sanger (“reference”) Sequence. If the optimal alignment from this process was present within the sequence window in which a CDR3 was predicted to exist, the CDR3 read configuration was classified as “compatible.” This “compatibility” scoring system was then compared to the read counts of the appertaining TRSeq configuration to generate a ROC curve.

FIG. 3-15: Coverage ROC Curve. Classification by expected specimen clonality, with curves for each coverage metric included, defined by varying gene coverage counts, as indicated in the legend.

FIG. 3-16A: Dilution Experiment Curve by V-J Configurations. In this experiment, mean raw read counts (+/− standard deviation) of the various Jurkat-specific V-J combinations are tallied for each of the dilutions.

FIG. 3-16B: Dilution Experiment Curve by V-J Configurations, Excluding Dilution 1. In this plot, the data from FIG. 3-16A are re-analyzed after excluding dilution 1, in order to highlight an apparently linear correlation between raw read counts and expected number of Jurkat cells at the lower end of the dilution series.

FIG. 3-17: Dilution Experiment Curve by Clonotype. In this experiment, mean raw read counts (+/− standard deviation) of the various Jurkat-specific clonotypes (i.e. V & J-gene & specific CDR3 sequence), allowing for acceptable CDR3 sequence error per the methods of Bolotin, et al. (27), are tallied for each of the dilutions.

FIG. 3-18: NTRA-BIOMED-2 Comparison. ROC analysis for classification by maximum TRB and TRG dominant clonotype read count-to-background ratio relative to overall BIOMED-2 results (taken as positive or negative for a clonal population).

FIG. 3-19: Coverage ROC Curve: Classification by BIOMED-2 Clonality Assessment. Cut-offs vary by coverage, as set-out in the legend.

FIG. 3-20: Unsupervised NMF clustering of V-J gene combinations. Red highlighted samples represent malignant entities, whereas green highlighted samples represent clonal but non-malignant entities. Colors are arbitrarily assigned to the four cluster designations.

FIG. 3-21: Volcano Plot: V-J gene combination usage differences between those cases classified as “clonal” and “polyclonal” by the BIOMED-2 assay. (the top enriched (right) and depleted (left) V-J combinations from each applicable locus are highlighted).

FIG. 3-22: Volcano Plot: V-J gene combination usage differences between malignant and non-malignant BIOMED-2-clonal cases. (the top enriched (right) and depleted (left) V-J combinations from each applicable locus are highlighted).

FIG. 3-23: Volcano Plot: V-J gene combination usage differences between LGL and non-LGL T-LPDs. (the top enriched (right) and depleted (left) V-J combinations from each applicable locus are highlighted).

FIG. 3-24: Volcano Plot: V-J gene combination usage differences between malignant LGL and non-malignant LGLs. (the top depleted V-J combinations from each applicable locus are highlighted).

FIG. A3.4-1: Sankey plot of relevant CIHI DAD TLPD epidemiology. The TLPD cases are segregated by sex, diagnostic category, as well as age category in relative proportions.

FIG. A3.4-2: Cox Proportional Hazards Model Survival Curve: TLPD “survival” vs. “survival” of other hematolymphoid entities. Based on anonymized CIHI “survival” estimated by the difference in the de-identified DAD day of disposition from the reference day for all “new” diagnoses.

FIG. A3.4-3: Cox Proportional Hazards Model Survival Curve: PTCL, NOS “survival” vs. “survival” of other TLPDs.

FIG. 4: T cell receptor hybrid capture reflects expected clonal make-up of bulk blood cells, tumour infiltrating lymphocytes, T-cell cancer cell line.

FIG. 5: A custom Bash/Python/R pipeline is employed for analysis of paired read sequencing data generated by Illumina DNA sequencing instruments from the hybrid-capture products. This pipeline consists of four major steps: (1) Merging of the paired reads; (2) Identification of specific V, J, and D genes within the fragment sequence; (3) identification of the V/J junction position as well as the antigen specificity determining Complementarity Determining Region 3 (CDR3) sequence at this site; (4) Calculation and visualization of capture efficiency and clone frequency within and across individual samples.

FIG. 6: An overview of the CapTCR-Seq hybrid-capture method. (A) Hybrid-capture method experimental flow diagram. Fragments are colored based on whether they contain V-region targets (blue), J-region targets (red), D-regions (green), constant regions (yellow) or non-TCR coding regions (black). (B) V(D)J rearrangement and CDR3 sequence detection algorithm flow diagram. (C) Number of unique VJ pairs recovered relative to library DNA input amount for one-step V capture of A037 PBMC derived libraries. (D) A037 polyclonal human beta locus VJ rearrangements determined by CapTCR-seq. (E) A037 polyclonal human beta locus VJ rearrangements determined by a PCR-based profiling service. (F) Subtractive comparison between CapTCR-seq and PCR-based profiling service. Red indicates relative enrichment of indicated pair by CapTCR-seq while blue indicates relative enrichment of indicated pair by PCR-based profiling.

FIG. 7: Cell line and tumor isolate T-cell clonality. Boxes represent individual unique VJ pairs and box size reflects abundance in sample. Samples ordered by decreasing clonality. (A) Beta chain VJ rearrangements. (B) Gamma chain VJ rearrangements. (C) L2D8 Gp100 antigen specific beta locus VJ rearrangements determined by CapTCR-seq. (D) L2D8 Gp100 antigen specific beta locus VJ rearrangements determined by a PCR-based profiling service. (E) Subtractive comparison between CapTCR-seq and PCR-based profiling service. Red indicates relative enrichment of indicated pair by CapTCR-seq while blue indicates relative enrichment of indicated pair by PCR-based profiling.

FIG. 8: Clinical sample T-cell clonality. Boxes represent individual clones with unique VJ rearrangements and box size reflects abundance in sample. Clonality assessments are indicated as either green (clonal), red (polyclonal), or yellow (not performed). Samples are ordered left to right in terms of increasing CapTCR-Seq clonality with an asterisk indicating disagreement between CapTCR-Seq and BIOMED2 assessments. (A) Beta chain VJ rearrangements. (B) Gamma chain VJ rearrangements.

FIG. 9: (A) A037 healthy reference sample: Unique alpha chain VJ combinatorial counts. (B) A037 healthy reference sample: Unique beta chain VJ combinatorial counts. (C) A037 healthy reference sample: Unique gamma chain VJ combinatorial counts. (D) A037 healthy reference sample: Unique delta chain VJ combinatorial counts. (E) Comparison of unique VJ fraction prevalence between A037 samples assessed by ImmunoSEQ and CapTCR-seq. Each point represents fraction of total observed rearrangements for each V or J allele.

FIG. 10: (A) Alpha chain VJ rearrangements. Boxes represent individual unique VJ pairs and box size reflects abundance in sample. Samples are ordered left to right in terms of decreasing clonality based on prevalence of top clone. (B) Delta chain VJ rearrangements. Boxes represent individual unique VJ pairs and box size reflects abundance in sample. Delta rearrangements were not observed for all samples. Samples are ordered left to right in terms of decreasing clonality based on prevalence of top clone. (C) Sanger sequencing validation of individual VJ rearrangements from hybrid-capture sample data with the number of times the given VJ rearrangement was observed plotted on the y-axis. VJ rearrangements that failed to generate a dominant band upon PCR amplification tended to be those with low observation counts. Green: Amplicon observed; Blue: Amplicon observed weakly; Red: Amplicon not observed.

FIG. 11: (A) Alpha chain. Boxes represent individual VJ rearrangements and box size reflects abundance in sample. Samples are ordered left to right in terms of decreasing clonality based on prevalence of top clone. (B) Delta chain. Boxes represent individual VJ rearrangements and box size reflects abundance in sample. Samples are ordered left to right in terms of decreasing clonality based on prevalence of top clone. Delta rearrangements were not observed for all samples. (C) Subtractive comparison between polyclonal A037 and collective lymphoma data set alpha VJ rearrangements. Red indicates relative enrichment in capture data while blue indicates relative enrichment in lymphoma data. (D) Subtractive comparison between polyclonal A037 and collective lymphoma data set beta VJ rearrangements. Red indicates relative enrichment in capture data while blue indicates relative enrichment in lymphoma data. (E) Subtractive comparison between polyclonal A037 and collective lymphoma data set gamma VJ rearrangements. Red indicates relative enrichment in capture data while blue indicates relative enrichment in lymphoma data. (F) Subtractive comparison between polyclonal A037 and collective lymphoma data set delta VJ rearrangements. Red indicates relative enrichment in capture data while blue indicates relative enrichment in lymphoma data.

FIG. 12: Overview of the capture method. Panel 1: A representative TCR locus with unrearranged and rearranged V, D, J, C gene segments. Panel 2: The TCR locus when sheared and represented in a sequencing library. Panel 3: Subsetting of J-containing regions with the J-probe library. Panel 4: Removal (depletion) of non-rearranged V-containing regions from the library with the depletion-probe library. Panel 5: Subsetting of V-containing regions with the V-probe library. Panel 6: Final subsetted library.

FIG. 13: Comparison of different method variants in terms of yielded average unique CDR3 sequences (normalized to reads and library input).

FIG. 14: Comparison of different hybridization and capture temperatures in terms of yielded average unique CDR3 sequences (normalized to reads and library input).

FIG. 15: Comparison of different depletion clean-up steps in terms of yielded average unique CDR3 sequences (normalized to reads and library input).

FIG. 16: Comparison of different permutations of iterative captures in terms of yielded average unique CDR3 sequences (normalized to reads and library input).

FIG. 17: CD3+ T cell fraction dilution curve. Comparison of average unique CDR3 sequences (normalized to reads and library input) for samples with varying amounts of source material added to generate the library (10 ng-250 ng).

FIG. 18: PBMC fraction dilution curve. Comparison of average unique CDR3 sequences (normalized to reads and library input) for samples with varying amounts of source material added to generate the library (10 ng-250 ng).

FIG. 19: PBMC fraction cDNA dilution curve. Comparison of average unique CDR3 sequences (normalized to reads and library input) for samples with varying amounts of source material added to generate the library (5 ng-40 ng).

FIG. 20: A037 VJ repertoire saturation curve. All samples derived from a single patient blood draw. Samples are drawn on the X-axis and black dots represents the fraction of new VJ combinations not seen before in previous samples from left to right and graphed on the right axis. Blue curve represents total combined number of unique VJ combinations across all samples from left to right and graphed on the left axis (log). Red curve represents per sample number of unique VJ combinations graphed on the left axis (log).

FIG. 21: A037 CDR3 repertoire saturation curve. All samples derived from a single patient blood draw. Samples are drawn on the X-axis and black dots represents the fraction of new CDR3 combinations not seen before in previous samples from left to right and graphed on the right axis. Blue curve represents total combined number of unique CDR3 combinations across all samples from left to right and graphed on the left axis (log). Red curve represents per sample number of unique CDR3 combinations graphed on the left axis (log).

FIG. 22: Comparison of VJ beta locus repertoire for A037 sample derived from genomic DNA (panel 1) and from cDNA (panel 2). A subtractive heatmap is shown in panel 3 that shows differences in overall repertoire between the two samples. Red indicates deviation for genomic, while blue indicates deviation for cDNA.

FIG. 23: Prevalence comparison of the top 1000 beta locus CDR3 in the genomic DNA set compared with their prevalences in the cDNA set.

FIG. 24: Beta locus VJ repertoire of an adoptive cell transfer immunotherapy patient over time. Samples are indicated on the X axis ordered by date of sample. VJ clones are ordered in all samples according to prevalence in the TIL infusion product and the top nine most prevalent TIL infusion clones are colored.

FIG. 25: Nine most prevalent TIL infusion clones at the Beta locus of an adoptive cell transfer immunotherapy patient over time. Samples are indicated on the X axis ordered by date of sample.

FIG. 26: TCR signal from an unselected cDNA library (red) and the same library following capture CapTCR-Seq (blue). Samples are indicated on the Y axis, while unique CDR3 counts is graphed on the X axis (log).

FIG. 27: TCR total signal (VJ counts) and repertoire diversity (unique CDR3 counts) for all samples from five patients.

FIG. 28: TCR total signal (VJ counts) and repertoire diversity (unique CDR3 counts) for all tumor samples from five patients.

FIG. 29: Patient A: Stacked barplots of unique VJ rearrangements for alpha locus tumor (panel 1), beta locus tumor (panel 2), alpha locus baseline blood (panel 3), and beta locus baseline blood (panel 4). Each box represents a VJ rearrangement and box size corresponds to prevalence within sample (Y axis).

FIG. 30: Top ten most prevalent beta locus rearrangements from patient A tumor.

FIG. 31: Patient B: Stacked barplots of unique VJ rearrangements for alpha locus tumor (panel 1), beta locus tumor (panel 2), alpha locus baseline blood (panel 3), and beta locus baseline blood (panel 4). Each box represents a VJ rearrangement and box size corresponds to prevalence within sample (Y axis).

FIG. 32: Top ten most prevalent beta locus rearrangements from patient B tumor.

FIG. 33: Patient C: Stacked barplots of unique VJ rearrangements for alpha locus tumor (panel 1), beta locus tumor (panel 2), alpha locus baseline blood (panel 3), and beta locus baseline blood (panel 4). Each box represents a VJ rearrangement and box size corresponds to prevalence within sample (Y axis).

FIG. 34: Top ten most prevalent beta locus rearrangements from patient C tumor.

FIG. 35: Patient D: Stacked barplots of unique VJ rearrangements for alpha locus tumor (panel 1), beta locus tumor (panel 2), alpha locus baseline blood (panel 3), and beta locus baseline blood (panel 4). Each box represents a VJ rearrangement and box size corresponds to prevalence within sample (Y axis).

FIG. 36: Top ten most prevalent beta locus rearrangements from patient D tumor.

FIG. 37: Patient E: Stacked barplots of unique VJ rearrangements for alpha locus tumor (panel 1), beta locus tumor (panel 2), alpha locus baseline blood (panel 3), and beta locus baseline blood (panel 4). Each box represents a VJ rearrangement and box size corresponds to prevalence within sample (Y axis).

FIG. 38: Top ten most prevalent beta locus rearrangements from patient E tumor.

FIG. 39: Sample fractions within all patient A samples for top ten most prevalent VJ rearrangements in tumor. Alpha locus (panel 1), beta locus (panel 2), gamma locus (panel 3), delta locus (panel 4).

FIG. 40: Sample fractions within all patient B samples for top ten most prevalent VJ rearrangements in tumor. Alpha locus (panel 1), beta locus (panel 2), gamma locus (panel 3), delta locus (panel 4).

FIG. 41: Sample fractions within all patient C samples for top ten most prevalent VJ rearrangements in tumor. Alpha locus (panel 1), beta locus (panel 2), gamma locus (panel 3), delta locus (panel 4).

FIG. 42: Sample fractions within all patient D samples for top ten most prevalent VJ rearrangements in tumor. Alpha locus (panel 1), beta locus (panel 2), gamma locus (panel 3), delta locus (panel 4).

FIG. 43: Sample fractions within all patient E samples for top ten most prevalent VJ rearrangements in tumor. Alpha locus (panel 1), beta locus (panel 2), gamma locus (panel 3), delta locus (panel 4).

DETAILED DESCRIPTION

In the following description, numerous specific details are set forth to provide a thorough understanding of the invention. However, it is understood that the invention may be practiced without these specific details.

The advantages of high-throughput DNA sequencing technologies could potentially be applied to T-cell clonality testing. The nature of T-cell gene diversity, requiring the consideration of potential variability arising from four distinct gene loci, makes obvious the benefit of multiplexing; what has traditionally required multiple separate tests could be combined in a single reaction. The capacity of modern DNA sequencing technologies to query longer contiguous segments of DNA in greater quantities relative to traditional techniques also provides an opportunity to explore the potential meaning of TRA and TRB sequence rearrangements. Sequence-level data might afford a greater ease of assay result interpretation. Indeed, the generation of sequence-level data in a TRGR assay would likely be much more informative than gross estimates of DNA electrophoretic migration patterns when disease trends are being studied; the high-level analysis of such data might help the identification of heretofore hidden patterns of TR rearrangement in specific T-cell lymphoma subtypes. The issue of replicate numbers for establishing test sensitivity/specificity can be easily overcome by exploiting the high-throughput capacity of modern DNA sequencing platforms; for a comparable investment of time (and possibly cost), sequencing-based approach to TRGR could perform a greater number of individual tests, thereby potentially allowing a more statistically robust estimate of test performance.

Traditional sequencing uses PCR-based techniques to markedly amplify input template DNA, thus improving the sensitivity of detection during the sequencing step. Indeed, many sequencing-based technologies still perform directed library preparation using PCR-based techniques to isolate and sequence regions of interest⁽³⁸⁾. By this approach, one might employ specific primer sets to enrich for regions of interest in the library preparation step. In the context of TRGR, however, a primer-based approach to library preparation would be challenging: in order to provide the sufficient breath of coverage required to interrogate the status of the vast number of TR genes (especially in the TRA locus), a massive array of primers would be required. Although it is theoretically possible to prime multiple regions in tandem, previous data suggest that such an approach might open the door to the possibility of technical error (for a more thorough review of the details of these errors and the studies that have supported this evidence, see⁽³⁸⁾). In the context of TRGR, furthermore, a primer-based approach to library preparation introduces the possibility of allele dropout when the assay attempts to prime a rearranged gene based on the known germline configuration (an easily digestible review to this effect may be found here⁽³⁹⁾).

A paradigm shift away from PCR primer-directed amplification of genomic areas of interest was required for sequencing experiments aimed at large numbers of genes. Indeed most sequencing-based technologies rather employ the upfront production of vast libraries of template oligonucleotides followed by a series of template enrichment steps⁽³⁸⁾. These latter steps may simply involve the extraction of DNA of specific lengths or quality, or rather the focus may be to enrich DNA containing specific sequences of interest. In the latter scenario, when specific sequence motifs are enriched for during library preparation, the resulting sequencing data will be enriched for the sequences of interest. Additionally, using the above stepwise approach, library preparation may be generalized to permit the enrichment of specific sequences out of a mix of “all” sequences produced from the primary non-specific amplification step; it is easy to see how this approach may be used to permit multiple separate assays using different enrichment approaches applied to a single input library⁽⁴⁰⁾.

Hybrid capture is a form of library enrichment in which a library is probed for known sequences of interest using tagged nucleic acid probes followed by a subsequent “pull-down” of the tagged hybrids⁽³⁸⁾; for example, DNA probes tagged with biotin can be efficiently enriched when hybridization is followed by a streptavidin enrichment step^((38,40-43)). The biotin/streptavidin enrichment procedure is schematized in FIG. 2-1A. In reference to the assessment of TRGR, this approach has the advantage of enriching TR genes based on the available well-defined germline TR gene sequences, which can be performed in a massively parallel fashion using several hundred probes. Notably, this approach also allows for enrichment of rearranged sequences as the hybrid-capture probes can also hybridize to (and therefore enrich for) subsequences of the rearrangement product. This latter “pull-down” of rearranged TR genes would be difficult using a primer-only approach to library preparation.

Rather than restricting the assessment of test performance of the above DNA sequencing approaches to a pre-set (and potentially biased) sample of “malignant” and “benign” T-cell lymphoproliferative disorders, a more prudent sampling rubric might use a “real-world” series of consecutive samples taken from a population as similar to the “test population” as possible. In the context of TRGR validation, such a sample might consist of a series of consecutive tissue samples from patients being worked-up by a hematologist and submitted for molecular (i.e. T-cell clonality) assessment. The overall sample size could be established based on an estimate of the historical incidence of T-cell lymphomas in such a population, such that the total size of the sample is adequately large to include a sufficient “expected” number of clonal T-cell lymphoproliferative disorders.

In many validation studies, the final pathology diagnosis is used as the gold standard against which the novel test is measured⁽⁴⁴⁾. While not unreasonable, there are arguments against employing such an approach. Of foremost concern is the potential for diagnostic or interpretative error, by which “true positivity” of disease could be misappropriated⁽⁴⁴⁾. In the realm of T-cell lymphomas, given at least partly due to their rarity, the frequent lack of pathologist experience might make this problem more likely. Furthermore, evidence indicates that even when diagnoses are based on consensus or panel based interpretation, the possibility of diagnostic bias by dominant opinion should be considered⁽⁴⁵⁾.

When a single clearly-defined outcome measure does not exist (or is limited by bias), a composite gold-standard might be more appropriate⁽⁴⁶⁾. Composite gold-standards might include a number of individual test results or clinical observations logically combined to produce “positive” or “negative” composites⁽⁴⁶⁾; of key import is that (1) well-defined rules of composition be set out a priori and (2) the number of samples or subjects with each of the composite test results should be well-described⁽⁴⁶⁾. Ideally, all samples or subjects should be evaluated using each of the composite tests⁽⁴⁶⁾.

In order to best study a novel test of TLPDs, rather than limiting the reference test to the gold-standard BIOMED-2 T-cell clonality assay or to pathology diagnoses, a series of both individual and composite references might be considered. From the perspective of analytical validity, one might consider validating an sequencing-based TRGR assay using standard PCR techniques followed by Sanger sequence verification. Since the sequences of each of the TR V and J genes are known, forward and reverse primer sets for each V and J genes, respectively, identified by the capture and sequencing assay could be used to verify that the detected result is valid; this could be followed by Sanger sequencing to validate the result of the DNA sequencing result (with deference specifically to the CDR3 variability-defining region).

In another experiment, one might consider comparing a sequencing-based TRGR result to the BIOMED-2 result (with each test applied to all specimens under study). The primary limitation of this approach would be that the BIOMED-2 assay, as explained above, does not test for any TRA rearrangements; thus this comparison alone would be insufficient. Additional comparisons might involve assessment of the sensitivity and specificity of each of the BIOMED-2 and sequencing-based TRGR assays at identifying benign or malignant TLPDs. For this, a composite gold-standard including histologic features (i.e. pathology diagnosis), immunophenotypic features, additional molecular features (as available, e.g. cytogenetic changes), clinical observations (e.g. presence or absence of features of malignancy), and outcome results (e.g. significant deviation in individual patient survival from the median) might be considered. The clinical validity of the sequencing results could thus be assessed against the current diagnostic standard by means of a much more thorough evaluation.

T-cell lymphomas are cancers of immune cell development that result in clonal expansion of malignant clones that dominate the T-cell repertoire of affected patients. Therefore, clonality assessment of these cell populations is essential for the identification and monitoring of T-cell lymphomas. We have developed a hybrid-capture method that recovers rearranged sequences of T-cell receptor (TCR) chains from all four classes (alpha, beta, gamma, and delta loci) in a single reaction from an Illumina sequencing library. We use this method to describe the TCR V(D)J repertoire of monoclonal cancer cell lines, tumor-derived lymphocyte cultures, and peripheral blood mononuclear cells from a healthy donor, as well as a set of 63 clinical isolates sent for clinical clonality testing for suspected T-cell lymphoma. PCR amplification and Sanger sequencing confirmed cell line and tumor predominant rearrangements, individual beta locus V and J allele prevalence was well correlated with results from a commercial PCR-based DNA sequencing assay with an r² value of 0.94, and BIOMED2 PCR fragment size beta and gamma locus clonotyping of clinical isolates showed 73% and 77% agreement respectively. Our method allows for rapid, high-throughput and low cost characterization of TCR repertoires that will enhance sensitivity of tumor surveillance as well as facilitate serial analysis of patient samples with a quantitative read-out during clinical immunotherapy interventions.

In an aspect, there is provided, a method of capturing a population of T-Cell receptor and/or immunoglobulin sequences with variable regions within a patient sample, said method comprising: extracting/preparing DNA fragments from the patient sample; ligating a nucleic acid adapter to the DNA fragments, the nucleic acid adapter suitable for recognition by a pre-selected nucleic acid probe; capturing DNA fragments existing in the patient sample using a collection of nucleic acid hybrid capture probes, wherein each capture probe is designed to hybridize to a known V gene segment and/or a J gene segment within the T cell receptor and/or immunoglobulin genomic loci.

As used herein, “T-Cell Receptor” or “TCR” means a molecule found on the surface of T lymphocytes (or T cells), preferably human, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The TCR is a disulfide-linked membrane-anchored heterodimeric protein normally consisting of the highly variable alpha (α) and beta (β) chains expressed as part of a complex with the invariant CD3 chain molecules. T cells expressing this receptor are referred to as α:β (or αβ) T cells, though a minority of T cells express an alternate receptor, formed by variable gamma (γ) and delta (δ) chains, referred as γδ T cells. Each chain is composed of two extracellular domains: Variable (V) region and a Constant (C) region. The variable domain of both the TCR α-chain and β-chain each have three hypervariable or complementarity determining regions (CDRs). CDR3 is the main CDR responsible for recognizing processed antigen.

The terms “antibody” and “immunoglobulin”, as used herein, refer broadly to any immunological binding agent or molecule that comprises a human antigen binding domain, including polyclonal and monoclonal antibodies. Depending on the type of constant domain in the heavy chains, whole antibodies are assigned to one of five major classes: IgA, IgD, IgE, IgG, and IgM. Several of these are further divided into subclasses or isotypes, such as IgG1, IgG2, IgG3, IgG4, and the like. The heavy-chain constant domains that correspond to the difference classes of immunoglobulins are termed α, δ, ∈, γ and μ, respectively. The subunit structures and three-dimensional configurations of different classes of immunoglobulins are well known. The “light chains” of mammalian antibodies are assigned to one of two clearly distinct types: kappa (κ) and lambda (λ), based on the amino acid sequences of their constant domains and some amino acids in the framework regions of their variable domains. The variable domains comprise the complementarity determining regions (CDRs). The methods described herein may be applied to immunoglobulin sequences, including B-cell immunoglobulin sequences.

“V gene segments”, “J gene segments” and “D gene segments” as used herein, refer to the variable (V), joining (J), and diversity (D) gene segments involved in V(D)J recombination, less commonly known as somatic recombination. V(D)J recombination is the mechanism of genetic recombination that occurs in developing lymphocytes during the early stages of T and B cell maturation. The process results in the highly diverse immune repertoire of antibodies/immunoglobulins (Igs) and T cell receptors (TCRs) found on B cells and T cells, respectively.

The term “nucleic acid” includes DNA and RNA and can be either double stranded or single stranded.

The term “probe” as used herein refers to a nucleic acid sequence that will hybridize to a nucleic acid target sequence. In one example, the probe hybridizes to the RNA biomarker or a nucleic acid sequence complementary thereof. The length of probe depends on the hybridization conditions and the sequences of the probe and nucleic acid target sequence. In one embodiment, the probe is at least 8, 10, 15, 20, 25, 50, 75, 100, 150, 200, 250, 400, 500 or more nucleotides in length.

The term “adapter” as used herein refers a moiety capable of conjugation to a nucleic acid sequence for a particular purpose. For example, the adapter may be used to identify or barcode the nucleic acid. Alternatively, the adapter may be a primer which can be used to amplify the nucleic acid sequence.

The term “hybridize” or “hybridizable” refers to the sequence specific non-covalent binding interaction with a complementary nucleic acid. In a preferred embodiment, the hybridization is under stringent conditions. Appropriate stringency conditions which promote hybridization are known to those skilled in the art, or can be found in Current Protocols in Molecular Biology, John Wiley & Sons, N.Y. (1989), 6.3.1 6.3.6. For example, 6.0× sodium chloride/sodium citrate (SSC) at about 45° C., followed by a wash of 2.0×SSC at 50° C. may be employed.

In some embodiments, the method further comprises sequencing the captured DNA fragments, wherein the sequencing can be used to determine clonotypes within the patient sample. Various sequencing techniques are known to the person skilled in the art, such as polymerase chain reaction (PCR) followed by Sanger sequencing. Also available are next-generation sequencing (NGS) techniques, also known as high-throughput sequencing, which includes various sequencing technologies including: Illumina (Solexa) sequencing, Roche 454 sequencing, Ion torrent: Proton/PGM sequencing, SOLID sequencing. NGS allow for the sequencing of DNA and RNA much more quickly and cheaply than the previously used Sanger sequencing. In some embodiments, said sequencing is optimized for short read sequencing.

In some embodiments, the method further comprises amplifying the population of sequences using nucleic acid amplification probes/oligonucleotides that recognize the adapter prior to said sequencing.

In some embodiments, the method further comprises fragmenting DNA extracted from the patient sample to generate the DNA fragments.

In some embodiments, the ligating step is performed before the capturing step.

In some embodiments, the capturing step is performed before the ligating step.

The term “patient” as used herein refers to any member of the animal kingdom, preferably a human being and most preferably a human being that has AML or that is suspected of having AML.

The term “sample” as used herein refers to any fluid, cell or tissue sample from a subject which can be assayed for nucleic acid sequences. In some embodiments, the patient sample comprises tissue, urine, cerebral spinal fluid, saliva, feces, ascities, pleural effusion, blood or blood plasma.

In some embodiments, the patient sample comprises cell-free nucleic acids in blood plasma.

In some embodiments, the clonality analyses described herein may be use to track clonality across samples types.

In some embodiments, the hybrid capture probes are at least 30 bp in length. In a further embodiment, the hybrid capture probes are between 60 bp and 150 bp in length. In a further embodiment, the hybrid capture probes are between 80 bp and 120 bp in length. In a further embodiment, the hybrid capture probes are about 100 bp in length.

In some embodiments, the hybrid capture probes hybridize to at least 30 bp, preferably 50 bp, more preferably 100 bp of the V gene segment and/or J gene segment.

In some embodiments, the hybrid capture probes hybridize to at least a portion of the V gene segment and/or J gene segment at either the 3′ end or the 5′ end of the V gene segment and/or J gene segment respectively.

In some embodiments, the screening probes hybridize to at least a portion of the V gene segment.

In some embodiments, the screening probes hybridize to at least a portion of the V gene segment at the 3′ end.

In some embodiments, hybridizing comprises hybridizing under stringent conditions, preferably very stringent conditions.

In some embodiments, the collection of nucleic acid hybrid capture probes comprise at least 2, 5, 10, 20, 30, 80, 100, 300, 400, 500, 600, 700, 800 or 900 unique hybrid capture probes.

In some embodiments, the collection of nucleic acid hybrid capture probes is sufficient to capture at least 50%, 60%, 70%, 80%, 90% or 99% of known T-Cell receptor and/or immunoglobulin loci clonotypes.

In some embodiments, the hybrid capture probes are immobilized on an array.

In some embodiments, the hybrid capture probes comprise a label. In a further embodiment, the label is used to distinguish between sequences bound to the screening probes and unbound double stranded fragments, and preferably the capture is performed in solution.

In some embodiments, preparing the DNA fragments comprises extracting RNA from the patient sample and preparing corresponding cDNA.

In some embodiments, the method further comprises a depletion step, comprising depleting the DNA fragments of non-rearranged sequences using probes that recognize nucleic acid sequences adjacent to V and/or J gene segments in the genome. In some embodiments, the capturing of DNA fragments using V gene segment and J gene segment hybrid capture probes is performed in separate steps, and in any order with the depletion step, preferably in the following order: J gene capture, depletion, then V gene capture.

In an aspect, there is provided, a method of immunologically classifying a population of T-Cell receptor and/or immunoglobulin sequences, the method comprising:

-   -   (a) identifying all sequences containing a V gene segment from         the sequences of the DNA fragments by aligning the sequences of         the DNA fragments to a library of known V gene segment         sequences;     -   (b) trimming the identified sequences in (a) to remove any         sequences corresponding to V gene segments to produce a         collection of V-trimmed nucleotide sequences;     -   (c) identifying all sequences containing a J gene segment in the         population of V-trimmed nucleotide sequences by aligning the         V-trimmed nucleotide sequences to a library of known J gene         segment sequences;     -   (d) trimming the V-trimmed nucleotide sequences identified         in (c) to remove any sequences corresponding to J gene segments         to produce VJ-trimmed nucleotide sequences;     -   (e) identifying any D gene segment comprised in the VJ-trimmed         nucleotide sequences identified in (d) by aligning the         VJ-trimmed nucleotide sequences to a library of known D gene         segment sequences;     -   (f) for each VJ-trimmed nucleotides sequence identified in (d),         assembling a nucleotide sequence comprising the V gene segment,         any D gene segment, and the J gene segment identified in steps         (a), (e) and (c) respectively;     -   (g) selecting from the nucleotide sequence assembled in step (f)         a junction nucleotide sequence comprising at least the junction         between the V gene segment and the J gene segment, including any         D gene segment, the junction nucleotide sequence comprising         between 18 bp and 140 bp, preferably 40-100 bp, further         preferably about 80 bp;     -   and optionally (h) and (i):     -   (h) translating each reading frame of the junction nucleotide         sequence and its complementary strand to produce 6 translated         sequences; and     -   (i) comparing the 6 translated sequences to a library of known         CDR3 regions of T-Cell receptor and/or immunoglobulin sequences         to identify the CDR3 region in the DNA fragments.

Alternatively, step (h) may be searching the 6 translated sequences for flanking invariable anchor sequences to define the intervening T-Cell receptor and/or B-cell receptor CDR3 sequences encoded by the DNA fragments.

In some embodiments, the method further comprises, prior to step (a), aligning left and right reads of overlapping initial DNA fragments to produce the DNA fragments on which step (a) is performed.

In some embodiments, steps (a), (c), (e) are performed with BLASTn and step (i) is performed using expression pattern matching to known sequences and IMGT annotated data.

In an aspect, there is provided, a method of identifying CDR3 regions in T-Cell receptor and/or immunoglobulin sequences, the method comprising:

-   -   (a) identifying a V gene segment comprised in the immunoglobulin         sequence by aligning the immunoglobulin sequence to a library of         known V gene segment sequences;     -   (b) identifying a J gene segment comprised in the immunoglobulin         sequence by aligning the immunoglobulin sequence to a library of         known J gene segment sequences;     -   (c) if V and J gene segments are identified, then comparing the         immunoglobulin sequence to a library of known CDR3 regions of         T-Cell receptor and/or immunoglobulin sequences to identify any         CDR3 region in the immunoglobulin sequence.

Alternatively, step (c) may be if V and J gene segments are identified, then searching the immunoglobulin sequence for flanking invariable anchor sequences to define the intervening T-Cell receptor and/or immunoglobulin CDR3 sequences.

In some embodiments, wherein steps (a) and (b) are performed using the Burrows-Wheeler Alignment or other sequence alignment algorithm.

In some embodiments, wherein if a CDR3 region is identified in step (c), then the method further comprises determining whether the identified V and J gene segments could be rearranged in the same locus using a heuristic approach.

In some embodiments, wherein if a CDR3 region is not identified in step (c), then the method further comprises determining if a combination of V(D)J gene segments is present based on Smith Waterman Alignment scores.

In an aspect, there is provided, a method for characterizing the immune repertoire of a subject, the immune repertoire comprising the subject's T-Cell population, the method comprising any of the hybrid capture methods described herein, any of the algorithmic methods described herein, or any combination thereof.

Any of the methods described herein may be used to capture a population of T-Cell receptor sequences, for immunologically classifying a population of T-Cell receptor sequences or for identifying CDR3 regions in T-Cell receptor.

In an aspect, the methods described herein are for characterizing T-cell clonality for a disease in the subject.

In some embodiments, the T-Cell receptor sequences are from tumour infiltrating lymphocytes.

In an aspect, the methods described herein are for identifying therapeutic tumour infiltrating lymphocytes for the purposes of expansion and reinfusion into a patient and/or adoptive cell transfer immunotherapy.

In an aspect, the methods described herein are for monitoring T-cell populations/turnover in a subject, preferably a subject with cancer during cancer therapy, preferably immunotherapy.

In an aspect, the methods described herein are for characterizing the immune repertoire of a subject, the immune repertoire comprising the subject's B-Cell population.

In an aspect, the methods described herein are for capturing a population of B-Cell receptor sequences with variable regions within a patient sample, for immunologically classifying a population of B-Cell receptor sequences, or for identifying CDR3 regions in B-Cell receptor sequences.

In an aspect, the methods described herein are for characterizing B-cell clonality as a feature of a disease in the subject.

The present methods may be used in subjects who have cancer. Cancers include adrenal cancer, anal cancer, bile duct cancer, bladder cancer, bone cancer, brain/cns tumors, breast cancer, castleman disease, cervical cancer, colon/rectum cancer, endometrial cancer, esophagus cancer, ewing family of tumors, eye cancer, gallbladder cancer, gastrointestinal carcinoid tumors, gastrointestinal stromal tumor (gist), gestational trophoblastic disease, hodgkin disease, kaposi sarcoma, kidney cancer, laryngeal and hypopharyngeal cancer, leukemia (acute lymphocytic, acute myeloid, chronic lymphocytic, chronic myeloid, chronic myelomonocytic), liver cancer, lung cancer (non-small cell, small cell, lung carcinoid tumor), lymphoma, lymphoma of the skin, malignant mesothelioma, multiple myeloma, myelodysplastic syndrome, nasal cavity and paranasal sinus cancer, nasopharyngeal cancer, neuroblastoma, non-hodgkin lymphoma, oral cavity and oropharyngeal cancer, osteosarcoma, ovarian cancer, pancreatic cancer, penile cancer, pituitary tumors, prostate cancer, retinoblastoma, rhabdomyosarcoma, salivary gland cancer, sarcoma—adult soft tissue cancer, skin cancer (basal and squamous cell, melanoma, merkel cell), small intestine cancer, stomach cancer, testicular cancer, thymus cancer, thyroid cancer, uterine sarcoma, vaginal cancer, vulvar cancer, waldenstrom macroglobulinemia, and wilms tumor.

In embodiments relating to T-cells, the subject may have a T-cell related disease, such as a T-cell lymphoma.

T-cell lymphomas are types of lymphoma affecting T cells, and can include peripheral T-cell lymphoma not otherwise specified, extranodal T cell lymphoma, cutaneous T cell lymphoma, including Sézary syndrome and Mycosis fungoides, anaplastic large cell lymphoma, angioimmunoblastic T cell lymphoma, adult T-cell Leukemia/Lymphoma (ATLL), blastic NK-cell Lymphoma, enteropathy-type T-cell lymphoma, hematosplenic gamma-delta T-cell Lymphoma, lymphoblastic Lymphoma, nasal NK/T-cell Lymphomas, treatment-related T-cell lymphomas.

In other embodiments relating to B-cells, the subject may have a B-cell related disease, plasma cell disorder, preferably a B-cell lymphoma.

B-cell are types of lymphoma affecting B cells and can include, diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, marginal zone B-cell lymphoma (MZL) or mucosa-associated lymphatic tissue lymphoma (MALT), small lymphocytic lymphoma (also known as chronic lymphocytic leukemia, CLL), mantle cell lymphoma (MCL), DLBCL variants or sub-types of primary mediastinal (thymic) large B cell lymphoma, T cell/histiocyte-rich large B-cell lymphoma, primary cutaneous diffuse large B-cell lymphoma, leg type (Primary cutaneous DLBCL, leg type), EBV positive diffuse large B-cell lymphoma of the elderly, diffuse large B-cell lymphoma associated with inflammation, Burkitt's lymphoma, lymphoplasmacytic lymphoma, which may manifest as Waldenström's macroglobulinemia, nodal marginal zone B cell lymphoma (NMZL), splenic marginal zone lymphoma (SMZL), intravascular large B-cell lymphoma, primary effusion lymphoma, lymphomatoid granulomatosis, primary central nervous system lymphoma, ALK-positive large B-cell lymphoma, plasmablastic lymphoma, large B-cell lymphoma arising in HHV8-associated multicentric Castleman's disease, B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma, B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, AIDS-related lymphoma, classic Hodgkin's lymphoma and nodular lymphocyte predominant Hodgkin's lymphoma.

In an aspect, the methods described herein are for identifying therapeutic B-cells for the purposes of expansion and reinfusion into a patient.

In an aspect, the methods described herein are for monitoring B-cell populations/turnover in a subject, preferably a subject with cancer during cancer therapy, preferably immunotherapy.

In an aspect, the methods described herein are for detecting minimal residual disease, whereby TCR or immunoglobulin rearrangements may be used as a marker of disease.

In an aspect, there is provided a library of probes comprising the depletion probes in Table D or at least one of the V-gene and J-gene probes set forth in any of Tables 2.1, 4, B1, or B2.

In some embodiments, the clonality analyses described herein may be performed serially.

In some embodiments, the clonality analyses described herein may be used to distinguish between samples.

The advantages of the present invention are further illustrated by the following examples. The examples and their particular details set forth herein are presented for illustration only and should not be construed as a limitation on the claims of the present invention.

Example 1

Methods and Materials

Assay Development

Several important theoretical considerations were entertained during the design phase of our novel sequencing-based TRGR assay (heretofore referred to as the NTRA).

Unlike the current BIOMED approach, we wished to avoid a gene-specific primer-based approach to signal amplification. To accomplish this, we chose a “hybrid capture” target enrichment approach by which input genomic DNA containing the TR genes might be enriched (or “captured”) relative to other segments of the genome. Several methodological approaches to target enrichment already exist, with multiple commercially available and rigorously optimized kits capable of enriching nearly any well-defined gene target(s)^((47,48)).

The NTRA needed to be robust enough to accommodate sample types of variable DNA quality; this requirement reflects the clinical need to apply TRGR assays to a wide variety of specimens in a wide variety of contexts. Knowing that Formalin-fixed paraffin-embedded (FFPE) specimens typically contain degraded and often poor quality DNA (as such representing the “lowest common denominator” of specimen quality)⁽⁴⁹⁾, it was deemed necessary to specifically evaluate NTRA performance on FFPE specimens. Furthermore, the use of hybrid capture is also amenable to highly fragmented DNA specimens such as those from circulating cell-free DNA.

Likewise, the most useful NTRA should allow users to both accurately assess the “clonality” of an input sample (as can be done using BIOMED-2 based assays) but also fully characterize the clonotypes of constituent TRGR configurations. Thus it was essential that the NTRA not simply produce a binary “clonal” vs. “polyclonal” result but also provide a much more robust and quantitative data output, including the genes and CDR3 regions present within identified TRGR configurations.

We recognized that much of the utility of the NTRA would depend on the design of a robust bioinformatic analysis pipeline. Of note, at the time at which this project was undertaken, only a single widely-used pipeline existed (the International standard source for ImMunoGeneTics sequences & metadata (IMGT) V-QUEST system), mainly designed around 5′RACE PCR followed by Roche 454 sequencing⁽⁵¹⁾. As outlined below, several methodological and logistic motivations demanded a novel pipeline of our own design.

Current sequencing-based applications generally require that resultant sequence data (i.e. reads) be mapped to a reference (typically the genome of the organism of interest) using some form of alignment algorithm. Once this alignment is complete, secondary and tertiary tools are used to search for and catalogue sequence deviation from the reference. For our purposes, however, using the entire human genome as a reference map would be unnecessarily cumbersome, especially since the presence of closely juxtaposed V(D)J sequence within a single short (i.e. <500 basepairs (bp)) fragment of DNA is tantamount to evidence of TRGR. Furthermore, aligning to a single reference genome raises the informatics challenge of detecting gene rearrangements from a single alignment step. As such, a strategy of mapping sequence reads to only the reference genes in a parallel fashion (i.e. one mapping procedure to the V genes, and one separate mapping procedure to the J genes) was selected, along with an integrated TRGR detection algorithm

This strategy required the theoretical consideration that short sequence read input might result in excessive false negatives (i.e. artificially low TRGR detection rates). This problem might be mitigated, in theory at least, by ensuring that input DNA fragment lengths (and the resulting sequencing read lengths) are carefully set to within a reasonable range of sensitivity for the detection of TRGR in a given sequence. Since all possible TRGRs are combinatorially vast, this process could only be simulated using, for our purposes, an artificial test set of simply-concatenated sequences of all catalogued V, D, and J genes (a test set numbering 197400). By evaluating k-mer subsequences over a range of lengths (k), centred (without loss of generality) about the median of each artificial junction, an estimate of the sensitivity of TRGR detection for variable sequencing windows can be produced. This sequencing window can then be used as an “evidence-based” DNA insert length.

Insert Length Simulation

Appendix 2.0 outlines a MATLAB script designed to estimate the optimal DNA insert length (a value also generalizable to optimal shearing length and minimal Paired-end rEAd mergeR (PEAR)-assembled sequencing length) for the purposes of the NTRA. This optimum is subject to an important restriction: for our purposes, using the Illumina NextSeq platform, read lengths are limited to paired-ended reads of 150 bp each—this translates to <300 bp read lengths when paired-ends are joined by overlapping sequence (using, in our case, the PEAR algorithm⁽⁵²⁾). Briefly, the code produces a simulation read set of all possible combinations of V-D-J sequences by way of simple concatenation (with the caveat that a much larger diversity of sequence is found in nature stemming from alterations of junctional sequence by way of splicing inconsistencies); next, the algorithm selects a k-mer (of length from k=32 to 302, in intervals of 30 bp) from within each simulation sequence; the resulting k-mer (centred, without loss of generality, at the junction median) is then subject to Burrows-Wheeler Alignment algorithm (BWA) alignment against the known reference V and J genes (as in the TRSeq pipeline) to evaluate how well the k-mers of each of the artificial reads can be mapped to both V and J genes (representing bioinformatic identification of TRGR within the sequence in question). A histogram of percent detection vs. read length was then produced; analysis of those artificial V-D-J read combinations that could be reliably detected was also performed.

DNA Probe Design

We began by reviewing the sequence and metadata of all reference TR genes obtained by way of a (FASTA-formatted) data download from the IMGT database. All sequences were subjected to a series of Clustal W⁽⁵³⁾ alignment analyses to verify that sequence alignment was limited to known reference motifs (i.e. the J-gene F/W-G-X-G motif and V-gene conserved Cysteine⁽⁵⁴⁾) and to allele-to-allele overlap.

DNA probe design was then performed using the IMGT reference sequences (including all annotated V and J gene functional, pseudogene and open reading frame sequences) using the xGen Lockdown probe technology. Briefly, this technology is a hybrid-capture-based technology by which biotin-tagged DNA probes (complementary to known sequences/genomic regions set at a 1× depth of coverage) are allowed to hybridize with sample DNA, followed by a streptavidin elution procedure performed to enrich the target sequences⁽⁴⁰⁻⁴³⁾.

In line with previous studies employing xGen Lockdown probes⁽⁴⁰⁻⁴³⁾, each DNA probe was designed to a length as close to 100 bp as possible. Using the IMGT database, germline-configuration sequences were extracted for all alleles of all J-genes, with additional leading and trailing IMGT nucleotides added (as necessary) to obtain 100 bp probe lengths; for those instances in which the IMGT data was insufficient to prepare 100 bp probes, additional random nucleotides were added to the leading and trailing ends of the available sequences. Again using the IMGT database, germline-configuration sequences were extracted for all alleles of all V-genes, with additional leading and trailing IMGT nucleotides added to ensure that the 5′ and 3′ ends of the germline-configuration genes were covered by a given probe (this design, it was theorized, would be able to account for gene re-arrangement at either end of a V-gene, regardless of strandedness, while still covering the vast majority of the sequence of each gene/allele). With careful placement of the probes as outlined above, we hoped that this design would also limit any specific stoichiometric bias among the V-genes represented in the target pool.

Table 2.1 outlines the complete list of xGen Lockdown probe design sequences (with relevant associated metadata).

NTRA Work-Flow

The NTRA work-flow is summarized in FIGS. 2-1A & 2-1B. Briefly, the process begins with DNA isolation, performed for the purposes of this study according to the protocol of Appendix 2.1. Isolated DNA was retrieved from frozen archives and quantified using the Qubit assay, per Appendix 2.2. Input DNA was shorn using a Covaris sonicator (Appendix 2.3) set to a desired mean DNA length of 200 base pairs; adequate shearing was confirmed using TapeStation assessment. Sequence libraries for each specimen were prepared using the protocol outlined in Appendix 2.4; multiplexing was accommodated using either TruSeq or NEXTflex-96 indices (the latter employed in the final validation run to permit large-scale multiplexing). Library preparation results were validated relative to input short DNA using TapeStation assessment. Subsequently, hybrid-capture with the above described xGen Lockdown probes was performed; captures were performed in pools of 9-13 input libraries, based on a pre-calculated balance of input DNA. The captured library fragments were then repeat-amplified, followed by final Qubit and TapeStation QC-steps. Finally, paired-end 150-bp sequencing was performed on the Illumina NextSeq platform using either a mid- or high-output kit (depending on sample throughput), according to the manufacturer's instructions (Appendix 2.5). The resulting read-pair zipped FASTQ-formatted data files were de-compressed and merged using the publically available PEAR alignment algorithm using a minimum of 25 bp overlap; this allowed the 150-bp sequencing maximum to be expanded to at least 200 bp, as suggest by the results of Section 2.1.2. Non-paired results were also tallied as a means of quality assurance. Subsequent analyses were performed using the custom-designed TRSeq analysis pipeline, as described below.

NTRA Data Analysis: The TRSeq Pipeline

The NTRA TRSeq pipeline was designed around three main algorithmic steps. The first performs local alignment indexed to the TR V and J genes implemented using the Burrows-Wheeler-Alignment (BWA) algorithm⁽⁵⁵⁾. From this algorithm, two important results are obtained: the first is a “reads-on-target” estimate (since the genes enriched for (i.e. the TR V and J genes) are those genes used as the index reference gene set); second, by way of the resulting Sequence Alignment Map (SAM) file output, the original input reads are filtered to exclude those unlikely to contain any of the TR V or J genes. This latter step reduces the informatic burden of input to the (relatively computationally slow) second algorithm step (using either heuristics or the Smith-Waterman Alignment (SWA)). Of note, the BWA algorithm could be implemented on a UNIX-based platform only⁽⁵⁵⁾.

The second algorithm step is designed to extract CDR3 sequences wherever present. This algorithm was implemented in MATLAB, guided by previous publications⁽⁵⁶⁾, and using a regular-expression (regexp) based search algorithm.

The third step combined the above alignment and CDR3 data (where present), to decide whether a given read contains a TRGR. To do this, one of two decision approaches is used: if a CDR3 is identified in a read, a heuristic approach is employed to decide if the BWA-alignment reference genes could be rearranged within the same locus; the second, in the event that a CDR3 is not detected, relies on the SWA-determined alignment scores to determine if a given combination of V(D)J genes is present.

Bioinformatic Target Enrichment (Burrows-Wheeler-Alignment Algorithm)

Much like the technical aspects of the NTRA function to enrich TR genes at the DNA level, so too can an informatics target-enrichment approach be employed. Using the BWA algorithm⁽⁵⁵⁾, a series of FASTQ-formatted reads are first mapped relative to a reference index of IMGT TR V and J genes. Any reads containing sequence mapping to any of the reference genes are flagged as such in the SAM-formatted output file as mapped, whereas those not containing any TR V or J gene mapped sequence are assigned the SAM Flag 4. In this context, unmapped reads are unlikely to contain any detectable TR V(D)J gene rearrangements; this predicate is logical inasmuch as sufficient residual germline sequence of a TR V and/or J gene are required in a read to permit TRGR detection.

Reads-on-target and gene-coverage estimates are also derived using the BWA algorithm, since NTRA input probes consist only of TR V and J genes; this measure is calculated as a percentage of the number of unique reads mapped to the IMGT reference TR V and J gene indices relative to the total number of reads in the input FASTQ-formatted file.

CDR3 Sequence Extraction and SWA Alignment

This part of the TRSeq algorithm was implemented in MATLAB using strategies similar to those employed by the IMGT⁽⁵⁶⁻⁵⁸⁾. The IMGT/V-QUEST system utilizes a CDR3 sequence extraction algorithm^((57,59)) and an SWA⁽⁶⁰⁾ algorithm performed against the IMGT reference sequences; the IMGT algorithms are all implemented in JAVA and processing is performed on IMGT servers.

As highlighted previously, we were unable to rely solely on the IMGT system for informatics results for several reasons: (1) the export of patient sequence data to an external non-secured network can be risky if insufficiently censored identifying metadata are also included; (2) the IMGT/High V-Quest system has a 500,000 sequence input limit (which may be substantially less than the number of sequence reads that need to be analyzed in the run of even a single high-throughput sequencing run); and (3) the queueing used by the IMGT can be lengthy, requiring a wait of possibly several days for sequence interpretation to begin.

A MATLAB implementation was chosen for convenience, programming familiarity, and because of easy vectorization, parallel computation and object-oriented programming capabilities. In addition, the MATLAB programming and command-line environments are able to easily incorporate UNIX and PERL-based scripts, including the BWA^((LL 2009)) and CIRCOS software⁽⁶¹⁾ suites, respectively.

The full coding of the analysis algorithm is presented in Appendix 2.6.2. The MATLAB code was written to accommodate FASTQ-formatted data, align each read using BWA to the reference TR V and J gene germline sequences, index the resultant data, test each indexed read for (and extract if present) a CDR3 sequence (using the uniformly present C-X(5 . . . 21)-F/W-G-X-G amino acid motif, per the IMGT canonical sequence motif^((62,63))), and perform either an heuristic or SWA alignment-based validation of the reads mapped by BWA as evidence of a rearrangement within the read in question.

The SWA algorithm produces an optimal local alignment^((60,64)) of two co-input sequences (in this case, a query sequence relative to an IMGT reference sequence), and provides an alignment score (a unit-less measure of the degree to which the alignment perfectly matches an input sequence to its co-input sequence). For the purpose of this instance of the algorithm, for any case in which multiple possible alignments were produced, the alphabetical highest-scoring alignment was selected as the “correct” alignment, provided that this score was at least greater than the minimum cut-off score.

The minimum SWA alignment cut-off score was empirically determined for each of the three V, D, and J-gene gene groups using a large set of confirmed-negative sequences evaluated using the IMGT/HighV-QUEST system^((66,67)). The MATLAB code required for implementation of this algorithm is outlined in Appendix 2.6.1. A “practice” set obtained from the IMGT database^((66,66)) was also employed to test the pipeline, consisting of IMGT PCR-confirmed TRGR sequences with known V-D-J combinations and CDR3 sequences (see Section 3.1.3 for results of this practice set analysis).

Analytical Validation

A selection of 10 “First-Run” samples formed the basis of the analytical validation. These samples included 6 de-identified actual patient samples, obtained from flow-sorted peripheral blood specimens, tumour-infiltrating lymphocyte populations or in vitro cultures of lymphocytes. These samples were each subjected to flow-cytometric evaluation and cell-counting for basic immunophenotyping and cell-input consistency. In addition, four cell lines with known and well-described TR gene rearrangements (based on references cited by the IMGT database⁽⁶⁷⁾) were also included (i.e. Jurkat (Deutsche Sammlung von Mikroorganismen and Zellkulturen (DSMZ) ACC-282), SUPT1 (American Type Culture Collection (ATCC) CRL-1942), CEM (ATCC CCL-119) and MOLT4 (ATCC CRL-1582)).

A three-part analytical validation approach was employed. First, the results obtainable by analysis of the sequencing data using the IMGT/High V-Quest pipeline were directly compared with the results of the TRSeq pipeline. Next, a PCR & Gel Electrophoresis experiment was designed to confirm the presence of the upper 90^(th) centile of rearrangement configurations. Finally, the predominant rearrangements with accompanying TRSeq-identified CDR3 sequences were further Sanger-sequenced to validate this latter component of the NTRA analysis.

Comparison with IMGT Results

Given the limited input size capacity of the IMGT/High V-Quest system, a read-by-read comparison of a 10% random subset of the NTRA sequencing data was performed. From the IMGT analysis, a read was assumed to contain evidence of a rearrangement when the IMGT pipeline Junction analysis yielded an in-frame result. In addition, a read-by-read comparison of the alignment results (by gene name, for all V, D and J genes) was also performed.

PCR & Gel Electrophoresis Validation

A PCR-based experiment was deemed a reasonable orthogonal validation approach, given the gold standard BIOMED-2 assay methodology. Knowing that the number of possible rearrangements detected by the NTRA might be substantially large, the PCR validation was arbitrarily limited to those TRSeq-detected rearrangements in the upper 90^(th) centile (i.e. percent rearrangement of greater than 10% of total rearrangements). Given this restriction, however, to ensure an adequate denominator of reactions for comparative purposes, all PCR validation experiments were uniformly performed across all 10 first-run samples.

PCR validation primer sets were constructed modeling the standard V-D-J orientation of rearranged TR genes; specifically, the PCR forward primer was set in the V gene and the reverse primer set in the anti-sense strand of the J gene. For each TRSeq-identified rearrangement above 10% of total rearrangements, the V and J genes were identified and the IMGT primer set database searched for gene (not allele) specific primers. While the IMGT primer database did contain a number of suggested primers, many of the TR genes did not have an available appertaining primer. As a result, where necessary, the anticipated rearrangement sequence (containing the V gene sequence artificially positioned before the J gene) was used to derive custom primers using the NCBI Primer-Blast tool⁽⁶⁸⁾. Careful attention was paid to ensure that each resulting theoretical PCR product length was at least 100 bp (the lower limit of fragment size reliably detectable by standard gel electrophoresis) and that a sufficient amount of the anticipated CDR3 region sequence would be preserved in the PCR product. In addition, the theoretical product length was recorded as an approximate size reference for analysis of the resulting electrophoresis migration patterns.

All putative primer pairs were then re-submitted to Primer-Blast⁽⁶⁸⁾ to assess for the possibility of non-specific products; the final set of putative primers pairs was also evaluated using the UCSC in silico PCR algorithm⁽⁶⁹⁾ to confirm that no germline configuration products of less than 4 kb might be produced. Primer set physicochemical characteristics were evaluated using the IDT OligoAnalyzer Tool (v 3.1); Clustal W⁽⁵³⁾ alignments were used to identify significant primer sequence overlaps (Clustal W alignments note significant overlap of the TRGJ1 and TRGJ2 primers. This overlap was considered acceptable in order to define which of the TRGJ1 and TRGJ2 genes were present (given the presence of 5′ end non-homology). Since the PCR/electrophoresis results suggested the presence of both TRGJ1 and TRGJ2 positive products, the dominant TRGJ1 primer was selected for subsequent analyses and the TRGJ2 results excluded). The final primer-set sequences are listed in Table 2.2.

Custom primer set production was performed commercially by IDT and the forward and reverse primers were then mixed according to the design outlined in Appendix 2.7.2. PCR was performed in a 384-well plate on an Applied Biosystems Veriti thermal cycler using the Thermo Scientific 2× ReddyMix PCR Master Mix kit according to the manufacturer's instructions; several control reactions were included, as highlighted in Appendix 2.7.2. Gel electrophoresis was performed in a 96-well Bio-Rad Sub-Cell Agarose Gel Electrophoresis System (necessitating 4 separate runs); electrophoretic migration was referenced against an Invitrogen Tracklt 1 kb DNA ladder and visualized using ethidium bromide fluorescence, photographed in a Alphalmager Gel Imaging System. Electropherograms were digitally rendered, adjusted and composited using Adobe Photoshop CC 2014. The resulting electrophoretic results were used in Receiver-Operating Characteristic (ROC) curve analyses relative to the corresponding TRSeq normalized read counts.

Sanger Sequencing Validation

Based on the results of the above PCR & Gel Electrophoresis experiment, rearrangement-positive PCR products were purified using a QIAquick Spin PCR purification kit (100 bp to 1 kb range) according to the manufacturer's instructions (Appendix 2.7.3). Purified PCR products were then quantified by Qubit and 20 ng equivalent aliquots were taken (with an additional volume reduction step using a SpeedVac, as required, for large volumes). The corresponding primer of the original primer pair with the lowest melting point was then selected for the purposes of single-direction Sanger Sequencing (performed at the TOGA Sick Kids Hospital Sequencing Facility).

The resulting sequencing results were analyzed using the FinchTV v 1.4 software suite, with corrections to sequencing error and reverse-complement sequence corrections performed manually as required. The originating TRSeq CDR3 sequences were then compared to the “reference” Sanger Sequence result. This comparison was performed in two ways: first, a basic multi-alignment comparison was performed (using the multialign algorithm of the MATLAB Bioinformatics Toolbox); second, a k-mer based PHRED-quality adjusted comparison was performed.

For the k-mer based approach, for a given V and J gene configuration, the most frequently detected TRSeq CDR3 sequences were aligned to the corresponding Sanger Sequencing result. In this context the Sanger Sequencing results were taken to represent a “consensus” of sequence data produced over all possible V and J configuration CDR3 sequences for that V-J gene configuration (reflecting the possibility of variable TRGR subclones). As such, in order to adjust the Sanger sequencing results to account for the potential alignment of a non-dominant subclone, a quality-based alignment algorithm was employed, based on the methods of⁽⁷⁰⁾. Each input TRSeq CDR3 sequence was aligned along a progressive series of k-mers of the Sanger sequence using a custom quality-based alignment algorithm (code outlined in Appendix 2.8). For each alignment result, if the optimal alignment score occurred within the expected sequencing region (thereby representing an optimal alignment within a region of Sanger sequence expected to contain the actual CDR3 based on flanking primer sets), as outlined in Table 3.1A, the CDR3 sequence was classified as correct (and vice-versa). This classification was then used to perform ROC analysis to determine what number of TRSeq CDR3 sequence read counts might be considered a validated cut-off.

Coverage Analysis

In addition to the above validation results, more detailed assessment of NTRA technical performance was also performed. Specifically, given that the NTRA relies on target enrichment, an assessment of the gene coverage of the NTRA was required. In addition, given that much of the utility of the NTRA might relate to identifying clonal cell populations, it was necessary to assess the dynamic sensitivity of the NTRA to decreasing numbers of cells bearing specific TR gene rearrangement configurations and, conversely, assess how standardized read counts might correlate with approximate input cell numbers.

Coverage Dynamics by Specimen Clonality

Given the nature of TRGR, by which genomic components are excised upon rearrangement, we evaluated the coverage dynamics across the first-run specimens. This analysis served not only as a mean of qualitatively comparing how V and J gene coverage might be expected to vary in specific types of specimens, but also to evaluate which coverage metrics might be most predictive of specimen type (i.e. clonal vs not) and what specific cut-off criteria might be used to this effect. To do this, ROC-based analyses of mean overall and locus-specific coverage data for V and J genes was performed, as well as percent genes at least 100× for each of V and J gene types.

Negative Control Coverage Assessment

For the purposes of this project, a fully germline TR gene configuration was approximated using a cell lines of embryonic origin and a cell line that has been fully sequenced without any known/reported TR gene derangements. The former scenario was approximated using the HEK293 cell line (an embryonic kidney cell line; ATCC CRL-1573) and the latter using a Coriell cell line (whose genome has been well-characterized and is not known to contain TR rearrangements). Use of the latter cell line was incorporated given that, in our hands, this cell line had been previously and purposefully degraded by FFPE treatment, representing a scenario of TR gene coverage assessment in the context of degraded DNA.

Total genomic DNA was extracted from previously cultured HEK293 cells and FFPE treated Coriell cell cultures and subsequently subjected to the NTRA, as outlined in Appendices 2.1 to 2.5. Standard TRSeq analyses were performed for each sample, with special deference paid to the coverage results.

Dilution Series

A rigorous dilution series experiment, in the context of this project, might involve a flow-sort spike of cells with a known TR gene configuration into a population previously determined to be “polyclonal”; this might be approximated, for example, using a well-characterized cell line spiked into a population of lymphocytes obtained from normal blood. Rather than undertaking this more complex and expensive approach, an approximation of this dilution experiment was undertaken with DNA obtained from the Jurkat cell line spiked into a known-polyclonal lymphocyte population DNA isolate (the A037 sample; see Results section 3.2). Specifically, Jurkat DNA was spiked in at log-decrements (as outlined in Table 2.3) based on a lymphocyte total DNA complement assumed to be 0.7 pg, given the results of previous publications⁽⁷¹⁻⁷³⁾. The total DNA of each sample in the dilution series was verified (and compared to expected values) using a Qubit assay; the samples were then subjected to the NTRA, as outlined in Appendices 2.1 to 2.5. Standard TRSeq analyses were performed, with special deference to changes in the raw read counts of Jurkat-specific TRGR configurations across the dilution series.

Alternative Method and Algorithm

Hybrid-Capture Protocol

For T cell receptor (TCR) diversity and clonality analyses we investigated genomic DNA isolated from flow sorted T cells isolated by affinity magnetic bead isolation, peripheral blood mononuclear cells (PBMC) isolated from blood by density gradient separation, cell-free plasma DNA extracted from blood, or scraped and pelleted immortalized cell lines.

Isolated DNA is sheared to −275 bp fragments by sonication in 130 uL volumes (Covaris). DNA libraries are generated for illumina platform sequencing from 100-1000 ng of sheared DNA by ligation of sequencing library adaptors (NextFlex) using the KAPA library preparation kit with standard conditions. Libraries are visually assessed (Agilent TapeStation) and quantified (Qubit) for quality.

Hybridization with probes specifically targeting the V and J genes is performed under standard SeqCap (Roche) conditions with xGen blocking oligos (IDT) and human cot-1 blocking DNA (Invitrogen). Hybridization is performed either at 65 C overnight. The target capture panel consists of 598 probes (IDT) targeting the 3′ and 5′ 100 bp of all TCR V gene regions, and 95 probes targeting the 5′ 100 bp of all TCR J gene regions as annotated by IMGT (four loci, 1.8 Mb, total targeted 36 kb). Hybridization and capture can be performed as a single step with a combined V/J panel, as a single step with only the V panel, or as a three step process when non-rearranged fragment depletion is desired consisting of a V capture, then depletion, then J capture.

For depletion of non-rearranged fragments 500 ng-1000 ng of library is depleted by hybridization with a panel of 137 probes (IDT) targeting the 5′ 120 bp of selected TCR V gene region 3′ untranslated regions as annotated by IMGT (four loci, 1.8 Mb, total targeted 16.5 kb) and 131 probes (IDT) targeting the 5′ 120 bp of selected Ig V gene region 3′ untranslated regions as annotated by IMGT (three loci, 3.1 Mb, total targeted 15.7 kb). A modified and truncated SeqCap protocol is employed wherein following incubation with M-270 streptavidin linked magnetic beads (Invitrogen), the hybridization reaction is diluted with wash buffer I, beads are discarded and the supernatant is cleaned up by standard Agencourt AMPure XP SPRI bead purification (Beckman).

Algorithm

A custom Bash/Python/R pipeline is employed for analysis of paired read sequencing data generated by Illumina NextSeq 2500 instrument from the hybrid-capture products. Referring to FIG. 5, this pipeline consists of four major steps: (1) Merging of the paired reads; (2) Identification of specific V, J, and D genes within the fragment sequence; (3) identification of the V/J junction position as well as the antigen specificity determining Complementarity Determining Region 3 (CDR3) sequence at this site; (4) Calculation and visualization of capture efficiency and clone frequency within and across individual samples.

(1) 150 bp paired-end reads are merged using PEAR 0.9.6 with a 25 bp overlap parameter. This results in an approximate 275 bp sequence for each fragment and enhances the sensitivity of V,J,D gene detection using the subsequent search strategies.

(2) Individual BLAST databases are created using all annotated V, D, J gene segments from IMGT. These full-length gene sequences are the targets of the hybrid-capture probe panel.

Individual merged reads are iteratively aligned using BLASTn with an e value cut-off of 1 to the V database, J database then D database with word size of 5 for D segment queries. Trimming of identified V or J segments in the query sequence is performed prior to subsequent alignment to reduce false positives and increase specificity, particularly for the D gene query.

(3) In order to identify CDR3 sequences, the V/J junction position is extracted from the previous search data for those fragments containing both a V and J search result. 80 bp of DNA sequence flanking this junction is translated to amino acid sequence in all six open reading frames and sequences lacking stop codons are searched for invariable anchor residues using regular expressions specific for each TCR class as determined by sequence alignments of polyclonal hybrid-captured data from a healthy patient as well as TCR polypeptides annotated by IMGT.

(4) Calculation of capture efficiency (on-target/off-target capture ratio) is performed by aligning all recovered, merged reads to the human genome (BWA) and dividing the number of reads aligning to the TCR loci by the total number of reads. The total number of unique TCR clones is determined by finding the unique minimum set of V/J combinations and the number of occurrences of each is tabulated. This data is visualized using R as stacked bar charts to generate figures that can be quickly visually assessed on a sample-by-sample basis for monoclonal or polyclonal signatures or clinically relevant enrichment of particular clones.

Application of the Algorithm to Existing Sequencing Data

The custom pipeline is not dependent on our hybrid-capture protocol and can be performed on non-target captured whole genome or RNA-seq data. In this situation, an in silico capture is performed by extracting reads aligning to the four TCR loci (7:38250000-38450000, 7:141950000-142550000, 14:22000000-23100000) or Ig loci (chr2:89,100,000-90,350,000, chr14:106,400,000-107,300,000, chr22:22,350,000-23,300,000) from DNA (BWA) or RNA (STAR) sequence data (SamTools), followed by paired-end nucleotide sequencing data extraction (PicardTools). These reads are then inserted in to the previously described computational pipeline.

Results and Discussion

Informatics

Insert Length Simulation

FIG. 3-1A details the DNA Insert Length Simulation results. The analysis suggested a plateau of sensitivity of greater than 99.1% reached after 182 bp. For convenience, an adequately “evidence-based” insert length and informatics read length goal of 200 bp was chosen for the NTRA.

After further analysis excluded extra-locus V-D-J gene combinations (i.e. combinations not likely to result from rearrangements within the same TR locus), the number of missed combinations was reduced from 1752 to 80.

From among the above 80 intra-locus combinations, missed rearrangements originated only from among the TRB and TRG loci, with particular enrichment of TRBV6-2*01 and TRBV6-3*01 within the former (65 of 80) and enrichment of the TRGJ1*02 within the latter (15 of 80).

Analysis by phylogenetic sequence alignment (using the SWA alignment algorithm) within the TRBV6 group showed significant cophenetic linkage between the TRBV6-2*01 and TRBV6-3*01 genes (see FIG. 3-1B). Similarly, analysis by phylogenetic sequence alignment within the TRGJ gene group suggested significant cophenetic linkage between TRGJ1*02 and TRGJ2*01 (see FIG. 3-1C). These results suggest that combinations within the artificial read set involving either of these TRBV genes were likely misaligned to another TRBV gene (likely the next closest cophenetic “cousin,” TRBV6-2*02) and that the TRGJ1*02 gene was likely misaligned to the TRGJ1*01 gene. Of note, the observation of closer cophenetic linkage between TRBV6-2*01 and TRBV6-3*01 rather than between TRBV6-2*01 and TRBV6-2*02 (as would be expected for two alleles of the same TR gene) and of closer cophenetic linkage between TRGJ1*02 and TRGJ2*01 rather than between TRGJ1*01 and TRGJ1*02, suggests error on the part of the IMGT classification.

MATLAB SWA Score Cut-Off Determination

The results of the empirical V, D and J-gene MATLAB alignment score cut-off score experiment are presented in FIG. 3-2. This experiment employed the code presented in Appendix 2.6.1 run on a test set of 91375 Illumina sequencing reads obtained from anonymized myeloid leukemia samples enriched for sequences outside of the IG/TR loci. These sequences were “confirmed” negative for V, D, and J gene sequences using the IMGT/High V-QUEST system (Brochet et al., 2008; Giudicelli et al., 2011). Given an experimental number of sequencing reads of at least 1 million, a 6-sigma cut-off score for MATLAB TRSeq analysis suggests 53.23 for the V genes; 19.02 for the D genes; and 34.43 for the J genes. It is easily observed that the cut-off values increase respectively from D, to J, to V genes; this observation parallels the mean length of the reference sequences from D to J to V genes.

TRSeq Analysis of IMGT-Produced TRGR Sample Sequence Reads

A sample of 268 short read sequences was downloaded from the IMGT website. These sequences consist of a variety of previously characterized TR and IG gene rearrangements available for download in FASTA format. After re-formatting into FASTQ format (using arbitrary quality scores), the dataset was analyzed using the TRSeq pipeline. Of the 268 short read sequences, 55 were identified by the IMGT as containing TR genes (either V or J genes); to these reads, there was perfect (100%) TRSeq alignment concordance, both in relation to gene name and allele. The TRSeq algorithm identified 50 of the 55 reads as containing evidence of TRGR; the 5 remaining reads were identified by the IMGT as containing rearrangements within the TRD locus, each with a TRSeq CDR3 region correctly identified. These results suggest that the 5 TRSeq “false-negatives” were informatically rejected by the TRSeq algorithm based on insufficient TRD D-gene SWA alignment score values; this form of error is not alarming given the more stringent means by which the TRSeq SWA alignment score cut-off values were determined relative to the IMGT/High V-QUEST pipeline^((56,58)).

First-Run Results Summary

Table 2.5 outlines the flow-cytometric features of the 6 patient lymphocyte samples. These immunophenotypic features were in keeping with the lymphocyte sample sources of origin (also documented in Table 2.5), varying from normal patient peripheral blood mononuclear cells to highly immuno-sensitized lymphocyte cultures from tumour infiltrating lymphocyte specimens. Notably, the A037 sample served as a model of a “polyclonal” lymphocyte population whereas, for the purposes of qualitative assessment at least, the L2D8 sample could be immunophenotypically interpreted as highly “clonal” in nature.

In addition, model “clonal” samples were included, consisting of the Jurkat, CEM, SUPT1 and MOLT4 cell lines. Table 2.6 lists the previously documented rearrangements, as cited in the IMGT database⁽⁶⁷⁾.

Prior to target enrichment and sequencing, adequate quality control was assured, as documented by pre and post-library preparation TapeStation tracings (see FIG. 3-3). Post-target enrichment quality control was assured in the same manner.

Illumina NextSeq sequencing was then performed on Tapestation-normalized pooled input target-enriched DNA. The appertaining read-pair FASTQ-formatted zipped files were decompressed and the PEAR paired-end merging algorithm was run with a minimum strand sequence overlap of 25 bp. A breakdown of the PEAR results is shown in FIG. 3-4. The resulting PEAR-merged FASTQ-formatted read files were input to the TRSeq pipeline.

FIGS. 3-5, 3-6, and 3-7A & 3-7B summarize the TRSeq metadata for the first-run sample series, including input reads, reads-on-target, summary coverage statistics, and a histogram of read counts for the proportion of each locus contributing to identified TRGR's, respectively.

One important highlight is the variation in coverage seen across the 10 specimens relating to the D locus. As described in the introduction, since the D locus genes are sandwiched within the larger A locus, the D locus genes are often deleted upon A locus rearrangement. The coverage profiles of the D locus therefore paralleled this phenomenon with lower D locus coverage identified in the clearly clonal or oligoclonal samples relative to the polyclonal samples (e.g. L2D8 and cell line samples vs. A037 peripheral blood sample).

FIGS. 3-8A and 3-8B display composites of the circos plots obtained from the 10 first-run samples. Much as the coverage profiles differed across the samples (as seen in FIGS. 3-8C & 3-8D), the resulting circos plots demonstrated a clear aesthetic difference from polyclonal to clonal/oligoclonal samples, with emphasis on the number and relative width of the composite circos links (i.e. fewer and broader in width in the more clonal cases and vice versa). Also of note, the color distributions were distinctly different with the more polyclonal cases, containing a larger number of smaller-quantity “subclones” involving a more disparate number of TR genes.

Analytical Validation

IMGT/High V-Quest Comparison

The boxplots of FIG. 3-9 summarize the comparison of the IMGT/High V-Quest pipeline analysis to the TRSeq results. The degree of concordance of read-to-read interpretation with respect to identifiable rearrangements (as present or not identified) is excellent (99%), as is the degree of concordance of named D genes (99%). A lower degree of concordance is noted for named V and J genes (68% and 84%, respectively). These results may relate to different initial alignment algorithms employed, as well as different gene-identity cut-off values employed in the SWA algorithms of the IMGT/High V-Quest and TRSeq pipelines. In light of the results seen in Section 3.1.1, the possibility of V and J gene phylogenetic sequence misclassification in the publically-available IMGT sequence databases should also be considered as a possible contributing factor.

The high D-gene concordance relative to the V and J-gene values may relate to both the shorter reference sequences of the D-genes relative to the V and J genes, as well as the lower number of reference D-genes available for rearrangement. It is important to point out the possibility of a theoretical bias against D-gene identification in input reads, given that TRGR reads containing D-genes require 3 rather than 2 composite genes, which could be more difficult to detect in the context of restricted average read lengths. This consideration was brought to bear during the NTRA assay design phase (as described in Section 3.1.1), with the conclusion that adequate flanking 5′ and 3′ sequence would be available on average in the scenario of read input length of 200 bp or more to reliably identify reads containing V-D-J rearrangements.

PCR & Gel Electrophoresis

PCR primers were mixed according to the design of FIG. 3-10 and the results by Agarose gel electrophoresis are shown in FIG. 3-11. Note that results obtained from PCR reactions using the TRGJ2 reverse primer are excluded, as noted in Section 2.2.2. Two classification approaches may then be entertained, one based on dark-staining PCR bands only, and the other based on any staining (assuming bands to be of appropriate molecular weights, as set out in Table 3.1A). When these classifiers are compared with the read-count-normalized results of the TRSeq algorithm (as set out in Table 3.1A), the ROC curves of FIGS. 3-12A & 3-12B are obtained, respectively. In the former scenario, the ROC Area-Under-the-Curve (AUC)=0.91 and p-value <0.001, with a TRSeq normalized read count of 6.7 or more. Based on the results of FIG. 3-12B, a less stringent classification results in a reduced AUC=0.71 and p-value <0.001, with a TRSeq normalized read count of 1.7 or more.

Sanger Sequencing Results

FIG. 3-10 details those PCR reactions that were post-PCR purified and submitted for Sanger Sequencing. FIG. 3-13 denotes the alignment of each corresponding TRSeq CDR3 sequence (and associated raw read count) in relation to the manually-verified/corrected Sanger Sequencing Result; only those Sanger Sequencing specimens containing TRSeq-identified CDR3 regions, those of sufficient quality for interpretation, and those not rejected based on use of the TRGJ2 reverse primer were further considered.

As may be seen in FIG. 3-13, there appears to be a trend for each distinct primer configuration inasmuch as TRSeq-identified CDR3 sequence configurations having sufficient associated read counts, as suggested from Section 3.3.2, show the best contiguous alignments to the corresponding “reference” Sanger Sequences.

To better quantify this relationship, we utilized a k-mer based quality-score adjusted alignment analysis. For each relevant primer configuration, the corresponding CDR3 was aligned using PHRED-based quality-score adjustment across the length of the Sanger “reference” sequence. If the optimal alignment from this process was present within the sequence window in which a CDR3 was theoretically predicted to exist, the CDR3 read configuration was classified as “compatible.” The resulting classification analysis is represented by the ROC curve of FIG. 3-14 (AUC=0.832, p-value=0.006). Based on this analysis, the optimal TRSeq normalized read count cut-off is 4.9.

Coverage Analysis

Coverage Dynamics by Specimen Clonality

Using the qualitative data of Table 2.5, specimens were classified as either “clonal” or “polyclonal.” The resulting ROC curves for the various coverage metrics are shown in FIG. 3-15. Of note, a mean V-gene coverage assessment of the gamma locus appeared to suggest the highest non-unity AUC. Further, the ROC analysis suggested that a mean V-gene coverage of greater than/equal to 4366.4 showed optimal sensitivity and specificity (86% and 67%, respectively) for predicting whether a specimen was unlikely to be clonal. Care should be taken not to use these cut-off points without additional validation, however, given the low number of data points constituting the analysis. Rather, these data stand to suggest a need for further evaluation of the potential predictability of “clonal” status derived from coverage analysis within the gamma locus.

Negative Control Coverage Assessment

The NTRA was tested on samples of previously cultured HEK293 and Coriell cell lines; these analyses aimed mainly at estimating coverage ceilings for the NTRA, but also served as added negative control specimens (i.e. specimens known or expected not to contain any TRGRs).

Applying the PEAR algorithm⁽⁵²⁾ (with a minimum 25 bp forward-reverse read overlap) resulted in pairing of 83% of input reads in the HEK293 sample and 90% of input reads in the Coriell sample.

In both instances, the number of subsequently identified TRGR configurations did not meet the TRSeq cut-off criteria (TRGRs were identified in 0 of 5,729,205 total input reads in the HEK293 cell line and only 7 of 2,761,466 total input reads in the Coriell cell line). This was in keeping with the anticipated fully-germline configuration of each of these non-lymphoid origin cell types.

For the HEK293 cell line, the percent V and J genes at or above 100× coverage was 100%; the overall TR V gene coverage averaged 29960×; and the overall TR J gene coverage averaged 8789×.

For the Coriell cell line, the percent V and J genes at or above 100× coverage was 100%; the overall TR V gene coverage averaged 13379×; and the overall TR J gene coverage averaged 3925×.

Dilution Series

A dilution experiment was performed at log-reduction intervals, set up according to the design of Table 2.3, and adjusted according to Table 3.2 to account for Jurkat DNA concentration discrepancies. Three Jurkat cell line unique TRGR configurations were selected for inter-dilution comparison, namely the TRAV8-4-TRAJ3, TRGV11-TRGJ1 and TRGV8-TRGJ2 rearrangements identified & confirmed in Section 3.3. The above configurations were confirmed absent in the polyclonal (A037) sample. In addition, each of these configurations showed a specific dominant CDR3 sequence.

FIG. 3-16A details the mean of the raw read-counts (i.e. not normalized) across the three tracked V-J configurations (with error bars for standard deviation) vs. expected approximate Jurkat cell numbers (with adjustments for significant digits) from Table 3.2. An exponential trend line could be applied, with R-squared=0.9996.

Of note, when the extremum of the first dilution is excluded, the dilution curve is remarkably linear (as seen in FIG. 3-16B), but with a positive slope. This suggests a linear direct correspondence between read count and number of cells bearing a given V-J configuration at low levels.

In contrast to the reliable low-level detection by way of V-J configuration, detection narrowed to absolute clonotype (by including the CDR3 sequence) was limited to only the first three dilution specimens (i.e. sensitivity down to an approximated 1 in 125 cells; see FIG. 3-17).

This limited sensitivity speaks to the sensitivity of the TRSeq junction finder to sequencing error. Indeed, if even a single base is changed relative to the canonical regular expression required for detection of a CDR3 sequence, the junction finder will not identify the sequence correctly; likewise, any non-triplicate base insertion will not be detected as an in-frame CDR3 sequence. In contrast, since the TRSeq V and J gene enumeration scheme uses alignment-based algorithms, the TRSeq results relating to V and J gene enumeration are much more forgiving of higher the higher likelihood of sequencing error in clonotypes with low read counts, thus substantially improving the assay sensitivity for characteristically unique V-J gene configurations.

Support for these suppositions is echoed in part by previous work pertaining to core clonotype analyses⁽²⁷⁾. Indeed, when the proposed criteria of Bolotin, et. al.⁽²⁷⁾ for gathering low-level reads of similar but error-prone sequence into common core clonotypes are applied to the dilution experiment (implemented in Appendix 3), it is possible to identify reads comparable to the clonotypes described above in even the most dilute samples.

For example, running the code of Appendix 3 with the input core clonotype of the TRGV8-TRGJ2 configuration, and allowing for a maximum of 3 sequence mismatches, 3 or more reads of satisfactory clonotype can be identified in dilutions 2-5. If the number of sequence mismatches is increased to 4, reads of satisfactory clonotype can be identified in all dilutions (i.e. down to an estimated sensitivity of 1 in 185646 cells).

The importance of these results stems from the applicability of this form of core clonotype analysis to a more accurate identification of minimal-residual disease, for example, at very low levels with remarkable sensitivity, even in the absence of traditional primer-directed sequence enrichment⁽⁷⁷⁾.

NTRA—BIOMED-2 Comparison

In keeping with the general approach used to assess BIOMED-2 results, the NTRA TRB and TRG clonotype tables were analyzed to compare the ratio of the dominant clonotype read count relative to the “background” read count. The largest read count not satisfying the normalized TRSeq read count according to the results of Section 3.3 was taken as the background read count value; alternatively, in the case where the dominant clonotype did not satisfy the normalized TRSeq read count cut-off of Section 3.3, the next largest clonotype read count was taken as “background”. From among each of the TRB and TRG loci, the largest dominant clonotype-to-background ratios were compared to the overall BIOMED-2 results using a ROC analysis.

See FIG. 3-18; the ROC analysis result could be classified as “good”⁽⁷⁸⁾ with AUC=0.82, p-value <0.001. Of note, this AUC value appears comparable to those observed in Section 3.3. Of even more impressive note is that the ROC-suggested dominant clonotype-to-background cut-off value was also comparable to that outlined in the current BIOMED-2 TRGR assay interpretation guidelines⁽⁷⁹); indeed, the ROC analysis-suggested value of 3.4, which is effectively the median value of the “indeterminate” range of dominant peak-to-background ratios recommended for BIOMED-2 result interpretation⁽⁷⁹⁾.

Interestingly, when the above process was broken down into two separate comparisons of the TRB and TRG loci, the TRG locus was found to be the significant driver: the TRG locus comparison alone yielded a ROC AUC=0.81 (p-value <0.001) whereas the TRB locus comparison alone yielded a ROC AUC=0.60 (p-value=0.17).

NTRA Coverage Metrics—BIOMED-2 Comparison

As in Section 3.4, an analysis of coverage variation in relating to clonal status was undertaken (see also FIG. 3-19). In contrast to the results of Section 3.4, a far less significant series of areas-under-the-curve were observed from this analysis. The greatest AUC was noted by analysis of mean V-gene coverage (i.e. mean V-gene coverage over all four loci) with AUC=0.59, p-value=0.213.

Furthermore, the data from Section 3.4 suggested that analysis of coverage from the Gamma locus might be predictive of clonal status. Unfortunately, these hypotheses were not substantiated by way of the clinical validation set, from which the AUC for the TRG locus V-gene analysis and TRG locus J-gene analysis were 0.59 and 0.57, respectively.

The clear discordance between these results and those of Section 3.4 likely relates to several factors. First, the sample size in Section 3.4 is one-sixth that of the clinical validation set, making the results of Section 3.4 much more vulnerable to the effects of outliers. Second, the overall coverage in the analytical validation set was lower, owing to base-output restrictions using the mid-output NextSeq kit; as such, coverage correlations made in Section 3.4 might not necessarily be applicable to experiments performed using the high-output NextSeq kit. Thirdly, the clinical validation experiment was not subject to bias of assumption as to the clonality of each input specimen; rather clonality was specifically assayed using an orthogonal method.

SUMMARY

Described above is the first hybrid-capture-based T-cell clonality assay designed to assess clonality and provide clonotype data over all four T-cell gene loci. For this purpose, a custom MATLAB-based analysis pipeline was implemented using optimized object-oriented programming integrating the ultra-fast BWA alignment system and the aesthetically-pleasing circos-based genomic data visualization suite. The latter visualization was designed with current methods in mind, in which electropherographic plots serve as the primary means by which clonotypes are visualized.

Advantages of NTRA Over Traditional T-Cell Clonality Testing Assays

Not only can the NTRA identify clonotypes from all four loci, the use of hybrid capture makes the process platform-agnostic. The laboratory work-flow can be integrated into any standard library preparation work-flow with the addition of a single hybridization step, capable of enriching for sequences containing T-cell genes of a several specimens at a time. In addition, as part of laboratory work-flows already using a hybrid-capture approach for other purposes, the probes used as part of the NTRA are amenable to “spike-in” combined hybridization reactions, provided that there is no significant probe-set sequence overlap or complementarity.

In comparison to the current BIOMED-2 based clonality assays, the NTRA adds a dearth of extra data, especially as pertaining to clonotype data from the gene-rich alpha-locus. This locus has traditionally been too diffusely distributed within the genome to be amenable to primer-based amplification, a challenge easily overcome using a hybrid-capture approach. Akin to the requirements of the IMGT, the NTRA outputs a clonotype table containing data specific to the best aligned allele. In contrast, however, visualized data is restricted to gene-level only, thereby providing a means of visualization comparable to electropherographic output. In addition, included with the latter, is the in-frame CDR3 sequence (where detected), data currently not available using either standard PCR-based techniques or the mainstream sequencing-based solutions (e.g. Invivoscribe).

In addition to validating the wet-bench and informatics using a number of orthogonal approaches, the NTRA was also shown to be theoretically sensitive to low-level clonotypes. This latter observation is an important boon to the hybrid-capture approach, suggesting that carefully performed hybrid-capture methods can provide signal amplification comparable to flow-cytometric⁽⁸¹⁾ and molecular approaches⁽³²⁾⁽⁸²⁾⁽⁸³⁾.

Assay Cost & Efficiency Considerations

As highlighted in Section 3.8, the assay may be considered cost effective, depending on the specific scenario of interest. In addition, the use of a hybrid-capture approach allows for spike-ins of additional probes for other genomic regions of interest. This allows the possibility of running multiple assays from a single library preparation step, requiring only bioinformatic separation of the resulting enriched sequences.

Applications

Assessment of lymphocyte clonality is integral to the diagnosis of diseases and cancer affecting the immune system. In addition, sequencing of the T-cell repertoire of a patient has gained clinical value with the recent understanding of T-cell mediated recognition and destruction of neoplasms. Further, the development of adoptive cell therapy and recombinatorial engineering of T-cell receptors requires high-throughput molecular characterization of in vitro T-cell populations before transplant. PCR-based methods such as BIOMED-2 and Immunoseq are currently in use for TCR characterization however their costs and complexity remain barriers for clinical deployment requiring high-throughput multi-patient, multi-sample work-flows at low cost. We have therefore developed a hybrid-capture-based method that recovers rearranged TCR sequences of heavy and light TCR chains from all four classes in one tube per sample at low cost. TCR clonality and CDR3 prevalence can be rapidly assessed in a three-day turn-around time with an automated pipeline generating summary figures that can be rapidly assessed by clinicians.

Adaptive T-cell immunotherapy has become a field of great interest in the treatment of multiple solid-tumor cancer types. Non-childhood cancers, particularly those linked to chronic exposure of known carcinogens, are driven by the accumulation of mutations. Some of these mutations drive pro-tumorigenic changes, while others result in non-tumorigenic changes to proteins expressed by the carrier cell. During normal protein turnover these modified proteins are broken down in to short polypeptides and make their way to the surface of the cell in association with molecular surveillance molecules (MHC I). In this context these modified polypeptides are recognized as foreign neo-antigens by the host immune system, and in the context of other signals, lead to the activation of T-cells that direct the destruction of cells expressing these modified proteins.

It is now understood that many solid-tumours exist in a state where their presence recruits neo-antigen specific T-cell lymphocytes to the margins however further advance and effective destruction of the tumor is prevented by expression of checkpoint inhibition molecules on the tumor cell surfaces. Therefore immunotherapy has become a major area of advance in cancer therapy wherein such checkpoint inhibition molecules are masked through transfusion of antibodies. This allows recognition of tumor and its destruction by neo-antigen specific T cells. In order to further enhance such anti-tumor activity, tumor infiltrating lymphocytes (TIL) can be isolated from tumor biopsies and expanded in vitro, followed by subsequent transfusion in great numbers back in to the patient following immunodepletion to enhance transplant colonization thereby driving a durable antitumor response.

T-cell lymphocytes are fundamental to this process, however due to their exquisite specificity, only neo-antigen specific T-cells are capable of driving anti-tumor activity. As a result there is a need for molecular characterization of circulating T-cells in the patient before and after treatment, infiltrating T-cells in the tumor before and after treatment, and screening of expanded populations in vitro for safety and efficacy. Our method provides a high-throughput, low cost and rapid turn-around method for T-cell receptor characterization in order to facilitate clinical deployment and uptake of adoptive cell transfer immunotherapy.

This method is not only of use in immunotherapy applications, as any disease involving expansion of T-cell clones would benefit from its use. The symptoms of autoimmune diseases are driven largely by T-cell mediated cytotoxicity of “self” tissue and therefore the identification and expansion of specific T-cell clones can be monitored using this method. This method would also be useful to follow immune challenges such as infection or immunization in the development of anti-infectives or vaccines.

Example 2

There is also described herein a laboratory and bioinformatic workflow for targeted hybrid-capture enrichment of T-cell receptor loci followed by Illumina sequencing to assess the clonality of a range of specimens with variable T-cell clonal complexity as well as a set of 63 T-cell isolates referred for clinical testing at our institution.

Methods and Materials

Probe Design—

All annotated V, D, J gene segments were retrieved from the IMGT/LIGM-DB website (www.imgt.org⁹). The 100 bp of annotated 3′ V gene coding regions and up to 100 bp, when available, of annotated 5′ J gene coding regions were selected as baits. Probes with duplicate sequences were not included.

DNA Isolation—

CD3+ T cells were isolated by flow assisted cell sorting of PBMC populations separated from whole blood. Peripheral blood mononuclear cells (PBMC) were isolated from whole blood by centrifugation followed by DNA isolation with a Gentra Puregene kit (Qiagen) according to manufacturer protocol. In the case of fresh/frozen tissues, a Qiagen Allprep (Qiagen) kit was employed, according to the manufacturer's instructions. In contrast, for FFPE samples a previously optimized in-house approach was used. First, sample FFPE tissue blocks were cored with a sterilized Tissue-Tek Quick-Ray punch (Sakura) in a pre-selected area of representative tissue; alternatively, under sterile conditions, 10×10 μm DNA curls/unstained slides were obtained for each submitted block of FFPE tissue. In a fumehood, 400-1000 μL xylene was aliquot into each tube (volume increased for larger FFPE fragments), followed by vigorous vortexing for 10 sec, incubation in a 65° C. water bath for 5 min, and centrifugation at 13200 rpm for 2 min. The supernatant was then discarded and step an additional xylene treatment step was performed. Subsequently, addition of 400-1000 μL ethanol (volume adjusted for larger input tissue volumes) was performed, followed by vigorous vortexing for 10 sec, and centrifugation at 13200 rpm for 2 min. The supernatant was then discarded and the ethanol treatment step repeated. The resulting pellet was then dried using a SpeedVac (Thermo Scientific) for 5 min, after which 150 μL of QIAamp buffer ATL (Qiagen) was added, followed by 48-hour incubation at 65° C. with 50-150 μL of proteinase K (volume increased for higher input volumes). A final ethanol clean-up step was performed, as above, to produce a purified DNA product. Resuspension in TE buffer (Qiagen) was then performed.

Hybrid Capture—

Isolated genomic DNA was diluted in TE buffer to 130 uL volumes. Shearing to −275 bp was then performed on either a Covaris M220 Focused-ultrasonicator or E220 Focused-ultrasonicator, depending on sample throughput, with the following settings: for a sample volume of 130 μL and desired peak length of 200 bp, Peak Incident Power was set to 175 W; duty factor was set to 10%; cycles per burst was set to 200; treatment time was set to 180 s. In addition, temperature and water levels were carefully held to manufacturer's recommendations given the instrument in use.

Illumina DNA libraries were generated from 100-1000 ng of fragmented DNA using the KAPA HyperPrep Kit (Sigma) library preparation kit following manufacturer's protocol version 5.16 employing NEXTFlex sequencing library adapters (B100 Scientific). Library fragment size distribution was determined using the Agilent TapeStation D1000 kit and quantified by fluorometry using the Invitrogen Qubit.

Hybridization with probes specifically targeting V and J loci (Supplemental Table 3) was performed under standard SeqCap (Roche) conditions with xGen blocking oligos (IDT) and human Cot-1 blocking DNA (Invitrogen). Hybridization is performed either at 65 C overnight. The target capture panel consists of 598 probes (IDT) targeting the 3′ and 5′ 100 bp of all TR V gene regions, and 95 probes targeting the 5′ 100 bp of all TR J gene regions as annotated by IMGT (four loci, 1.8 Mb, total targeted 36 kb).

Capture Analysis—

A custom Bash/Python/R pipeline was employed for analysis of paired read sequencing data generated by Illumina NextSeq 2500 instrument from the hybrid-capture products. First, 150 bp paired reads were merged using PEAR 0.9.6 with a 25 bp overlap parameter^(A18). This results in a single 275 bp sequence for each sequenced fragment. Next, specific V, J, and D genes within the fragment sequence were identified by aligning regions against a reference sequence database. Specifically, individual BLAST databases were created using all annotated V, D, J gene segments retrieved from the IMGT/LIGM-DB website (www.imgt.org^(A9)), as these full-length gene sequences were the source of probes used to design the hybrid-capture probe panel. Individual merged reads are iteratively aligned using BLASTn with an e value cut-off of 1 to the V database, J database then D database with word size of 5 for D segment queries^(A19). Trimming of identified V or J segments in the query sequence is performed prior to subsequent alignment. From reads containing V and J sequences, we identified V/J junction position and the antigen specificity determining Complementarity Determining Region 3 (CDR3) sequences. In order to identify CDR3 sequences, the V/J junction position is extracted from the previous search data for those fragments containing both a V and J search result. 80 bp of DNA sequence flanking this junction is translated to amino acid sequence in all six open reading frames and sequences lacking stop codons are searched for invariable anchor residues using regular expressions specific for each TR class as determined by sequence alignments of polyclonal hybrid-captured data from rearranged TR polypeptides annotated by IMGT⁹

Results and Discussion

The CapTCR-seq method employs hybrid capture biotinylated probe sets designed based on all unique Variable (V) gene and Joining (J) gene annotations retrieved from the IMGT database version 1.1, LIGMDB_V12⁹. These probe sets specifically target the 3′ regions of V gene coding regions and the 5′ regions of J gene coding regions that together flank the short Diversity (D) gene fragment in heavy chain encoding loci and which together form the antigen specificity conferring CDR3 (FIG. 6A). D regions (absent in alpha and gamma rearrangements) were not probed due to their short lengths, high potential junctional diversity introduced by the recombination process, and to permit a single universal probe set for both light and heavy chain loci. These biotinylated probes are hybridized with a fragmented DNA sequencing library, and probe-target hybrid duplexes are subsequently recovered by way of streptavidin-linked magnetic beads. The subsetted library is PCR amplified from the bead-purified hybrid-duplex population using a single set of adapter-specific amplification primers and the resulting library is subjected to paired read 150 bp sequencing on an Illumina NextSeq 500 instrument. A 250 bp fragment size was selected as mid-range between the maximum length of a merged fragment from 150 bp paired-end read sequencing (275 bp) and a lower limit of 182 bp based on alignments of simulated reads centered at the VJ junction with variable insert sizes that had successful V and J alignment sensitivity of >99%.

To identify V(D)J rearrangements from the pool of captured V and J sequences, we used a computational method that performed: (1) Read merging to collapse paired reads in to a single long-read sequence to enhance V(D)J and CDR3 identification, (2) progressive BLASTn-based V, J and D detection utilizing iterative end trimming and (3) CDR3 scoring using regular expression pattern matching (FIG. 6B). This BLAST-based sequence alignment approach was employed due to its tolerance for nucleotide mismatches that could arise from junctional diversity or the presence of allelic variants not present in the reference database. We acknowledge that numerous alternative V(D)J and CDR3 calling algorithms are available^(A10-16) and these may be used in addition or in lieu of our pipeline to analyze V(D)J fragments captured by our laboratory approach. A head-to-head comparison of these methods is beyond the scope of this proof-of-principle report.

We employed this method to identify V(D)J rearrangements and CDR3 sequences in PBMCs isolated from a healthy human. With a single step hybridization and capture reaction employing the probe panel targeting TCR V genes, the number of detected unique VJ rearrangements increased with increasing amount of sample genomic DNA used to generate the initial library, with 52 times more rearrangements detected with an input of 1,000 ng compared with 100 ng (1925 vs 37) (FIG. 6C). The number of unique VJ rearrangements is dependent on the number of T cells in the original sample with an approximate fourfold increase for CD3+ sorted cells over PBMCs (2475 vs 759) (Supplemental Table 1). Addition of the J probe panel to form a single-step capture using a pooled V and J panel improved recovery of unique CDR3 sequences per 1 ng of library input by 5 fold (single-step V capture mean: 1.7, single-step VJ capture mean: 8.56) (Supplemental Table 1). This modification also increased the ratio of on-target reads, effectively decreasing the amount of sequencing needed to obtain the same number of rearranged fragments (single-step V capture mean: 14.4%, single-step VJ capture mean: 42.9%). Overall, we saw a diverse representation of alleles for all four classes with 2895 alpha, 1100 beta, 59 gamma, 9 delta unique VJ rearrangements observed from 16 independent captures of independent libraries (FIG. 9A-D). This corresponded to 6257 alpha, 4950 beta, 1802 gamma, 109 delta unique CDR3 sequences. We also submitted a portion of these samples for parallel characterization by a commercial PCR-based TCR profiling service and found similar V/J gene usage and representation with no more than 2% variation (FIG. 6D-F) and correlation with an r² value of 0.94 (FIG. 9E)

To test the ability of CapTCR-seq to assess TCR clonality of samples with a range of clonal signatures, we analyzed libraries derived from CD3+ flow-sorted Tumor Infiltrating Lymphocytes (TIL) expanded cultures (oligoclonal) and lymphoblast cell lines (clonal) (FIG. 7A-B; FIG. 10A-B). As expected, the cell-lines and antigen-specific cell-sorted samples were more clonal (12-22 unique VJ rearrangements) than the TIL cultures (123-446 unique VJ rearrangements). The predominant alpha rearrangement represented 40-80% of the recovered reads in clonal samples compared to 2.5-17.5% for the latter TIL cultures. Specifically, we detected 12 unique VJ rearrangements in L2D8, a GP100 antigen-specific tumor-infiltrating lymphocyte clone. In OV7, a mixed ovarian tumor-infiltrating lymphocyte population expanded with IL-2 treatment, we found 311 unique VJ rearrangements. We profiled two populations isolated from the same tumor: M36_EZM, a cell suspension of melanoma tumor with brisk CD3 infiltration harbored 123 unique VJ rearrangements, while M36_TIL2, tumor-infiltrating lymphocytes from this tumor expanded in IL-2 harbored 446 unique VJ rearrangements, reflecting a likely expansion of low prevalence T cells. STIM1 is MART1-specific cell line made from peptide stimulation of healthy donor PBMCs, FACS sorting and expansion of tetramer+ cells from which we found 195 unique VJ rearrangements. The cell lines were found to encode previously reported gene rearrangements at the TCR beta and gamma loci, and additional rearrangements not previously reported (Supplemental Table 2)^(A17). Targeted PCR amplification of V/J rearrangement pairs, including the most frequently observed for each sample, was performed on these samples. We observed expected product for all prevalent rearrangements with some amplification failures for low prevalence rearrangements (Sample: Observed bands/expected bands; A037: 9/11; L2D8: 4/5; EZM: 3/4; TIL2: 8/9; OV7: 5/9; STIM1: 7/9; SE14 2005: 4/4; SE14 2033: 3/4; SE14 2034: 4/4; SE14 2035: 4/4) (FIG. 100). We also submitted the GP100 antigen specific L2D8 sample for beta locus profiling by a PCR-based commercial service and found VJ repertoire usage to be highly congruent (FIG. 7C-E), however the commercial service identified extensive low level VJ gene usage not present in the capture data (FIG. 7D). This signal may represent low-level alternative VJ pair antigen specific clones, or sample contamination with non-antigen specific clones.

To demonstrate the potential clinical utility of our approach, we generated DNA sequencing libraries from an unselected cohort of 63 samples submitted for clinical T-cell receptor rearrangement testing and subjected these to capture, sequencing and analysis (Supplemental Table 1). Samples were found to have varying degrees of clonality, with the predominant CDR3 sequence representing up to 40% of the most clonal sample (average 12.2%; median 6.3%%, range 0.8-100%, FIG. 8A-B; FIG. 11A-B). When a clonal population was defined as having the most abundant to third most abundant rearrangements observed at two or more times the level of the next most abundant rearrangement, we observed three groups of samples: 11 with clonal enrichment of both beta and gamma rearrangements, 12 with clonal enrichment of beta or gamma rearrangements, and 41 that were polyclonal for both beta and gamma. When 61 of these samples were assessed by BIOMED2 assay we observed 73% agreement for beta (44/60) and 77% for gamma (46/60), 60% of samples were in agreement for both beta and gamma clonality measures (36/60). For the beta locus, 13 samples that were scored as clonal by BIOMED2 were scored as polyclonal based on relative prevalence when assessed by hybrid capture profiling. Six had low top clone prevalence (predominant rearrangement relative proportion of 1.3%, 1.8%, 2.6%, 3.1%, 3.4%, 3.8%) with a median unique VJ rearrangement count of 185. Seven had higher top clone prevalence (predominant rearrangement relative proportion of 7.6%, 8.4%, 8.5%, 8.8%, 11.9%, 12.1%, 16.9%) with a considerably lower median unique VJ rearrangement count of 44. These 13 samples had variable diversity but no predominant rearrangement was more than twofold enriched relative to the next most common rearrangement. Conversely, three samples that were scored as polyclonal by BIOMED2 at the beta locus were scored as clonal based on relative prevalence (predominant rearrangement relative proportion of 25.9%, 18.6%, 6.5%) with a median unique VJ rearrangement count of 191. These discrepancies could be resolved with deeper sequencing of these libraries to determine whether insufficient depth was distorting the interpretation or whether these represent incorrect interpretations by the BIOMED2 protocol. Improvements in the BIOMED2 primer sets have led to reduced false positives compared to previous generations, and can be further diminished through the use of higher resolution gel separation and additional analyses^(A2), however if available, sequencing-based methods provide a more quantitative assessment and relative comparison between all rearrangements. To determine whether there was unexpected enrichment in the A037 or lymphoma data sets we compared their gene usages (FIG. 11C-F). A037 and the lymphoma collection had similar VJ usage profiles with few individual unique VJ rearrangement proportion enriched in A037 of up to 1% and more enrichments amongst the lymphoma set of up to 3% as expected given the clonal enrichment of select rearrangements in T-cell lymphomas.

In summary, CapTR-Seq allows for rapid, inexpensive and high-throughput profiling of all four loci from multiple samples of diverse types from a given DNA sequencing library with fragment size of 250 bp and sequencing length of 150 bp. This method will permit intensive monitoring of TR repertoires of patients with T-cell malignancies as well as monitoring of tumor-infiltrating lymphocytes in tumors from patients undergoing immune checkpoint blockade, adoptive cell transfer and other immunotherapies.

Example 3

Adoptive Cell Transfer (ACT) of in-vitro expanded Tumour-Infiltrating Lymphocytes (TIL) has emerged as an effective treatment for numerous types of solid tumours, often resulting in a durable response and in some cases a complete remission by the patient^(B1). This intervention effectively replaces nearly the entire heterogenous T-cell repertoire of the patient with tumour antigen and patient-specific effector T cells. Effector T-cells are integral for the adaptive immune response due to their roles in cellular cytotoxicity and cytokine production, with specificity conferred by the TCR-MHC interaction^(B2). The CD8+ effector T-cell repertoire consists of alpha/beta and gamma/delta subtypes, both polyclonal and skewing in the incidence of an antigen-specific response or malignancy^(B3). In high mutation load neoplasms, the MHC molecule often presents tumour-associated neo-antigens generated as a result of mutation that lead to clonal expansion and infiltration of tumour-infiltrating lymphocytes (TILs)^(B4). These TILs are largely clonal and distinct from the circulating repertoire in multiple types of neoplasia^(B5). While these TILs are capable of driving an effective anti-tumour response in vitro, they are often exhausted within the tumour microenvironment as a result of expression of immunosuppressive cell-surface proteins by the tumour but their activities can be restored with immune checkpoint blockade therapy^(B6). The combined effect of immunotherapy intervention: immunodepletion, TIL ACT and checkpoint blockade together present an effective treatment for many patients but have a disruptive effect on the endogenous immune repertoire and therefore proper patient care would benefit from longitudinal monitoring of the T-cell repertoire during the course of disease and treatment.

During ACT immunotherapy, both the requisite immunodepletion and T-cell transfer radically disrupt the abundance and diversity of the endogenous T-cell population and therefore molecular profiling methods are required for monitoring of the patient during the course of immunotherapy^(B7). The TCR repertoire consists of cell-specific heterodimeric receptors uniquely rearranged and expressed from either the alpha/beta or gamma/delta genomic loci^(B8). The TCR has unique specificity for an antigen presented in the context of the an MHC molecule as defined by the combined interactions of the amino acid residues encoded at the V-(D)-J junction known as the complementarity determining region 3 (CDR3), and by the CDR1 and CDR2 regions in the upstream V gene fragment.

Methods and Materials

Probe Design—

All annotated V (V-panel), D, J (J panel) gene segments and V 3′-UTR (depletion panel) sequences were retrieved from the IMGT/LIGM-DB website (www.imgt.org). The 100 bp of annotated 3′ V gene coding regions, up to 100 bp, when available, of annotated 5′ J gene coding regions, and 120 bp of V 3′-UTR sequences were selected as baits. Probes with duplicate sequences were not included. The V-panel consists of 299 probes (IDT) targeting the 3′ and 5′ 100 bp of all TR V gene regions, and the J-panel consists of 95 probes targeting the 5′ 100 bp of all TR J gene regions as annotated by IMGT (four loci, 1.8 Mb, total targeted 36 kb). The depletion-panel consists of 131 probes targeting the 5′ 120 bp of 3′-UTR Immunoglobulin V regions, and 107 probes tareting the 5′ 120 bp of 3′-UTR TCR V regions.

DNA Isolation—

CD3+ T cells were isolated by flow assisted cell sorting of PBMC populations separated from whole blood. Peripheral blood mononuclear cells (PBMC) were isolated from whole blood by centrifugation followed by DNA isolation with a Gentra Puregene kit (Qiagen) according to manufacturer protocol. In the case of fresh/frozen tissues, a Qiagen Allprep kit (Qiagen) was employed to extract DNA and RNA, according to the manufacturer's instructions. The whole blood plasma fraction was then treated with red blood cell lysis buffer and circulating DNA (cfDNA) was extracted using the Qiagen Nucleic Acid kit (Qiagen) according to manufacturer protocol.

cDNA Synthesis—

mRNA was separated from isolated total RNA using the NEBNext Poly(A) mRNA Magnetic Isolation Module (NEB) according to manufacturer's instructions. To generate cDNA, first NEBNext RNA First Strand Synthesis Module (NEB) was used followed by NEBNext RNA Second Strand Synthesis Module (NEB) according to manufacturer's instructions.

Library Preparation—

Isolated genomic DNA or synthesized cDNA was diluted in TE buffer to 130 uL volumes. Shearing to −275 bp was then performed on either a Covaris M220 Focused-ultrasonicator or E220 Focused-ultrasonicator, depending on sample throughput, with the following settings: for a sample volume of 130 μL and desired peak length of 200 bp, Peak Incident Power was set to 175 W; duty factor was set to 10%; cycles per burst was set to 200; treatment time was set to 180 s. In addition, temperature and water levels were carefully held to manufacturer's recommendations given the instrument in use.

Illumina DNA libraries were generated from 100-1000 ng of fragmented DNA using the KAPA HyperPrep Kit (Sigma) library preparation kit following manufacturer's protocol version 5.16 employing NEXTFlex sequencing library adapters (B100 Scientific). Library fragment size distribution was determined using the Agilent TapeStation D1000 kit and quantified by fluorometry using the Invitrogen Qubit.

Hybrid Capture—

For cDNA derived libraries, hybridization was performed with a pooled panel of probes targeting V and J loci in equimolar concentrations. For genomic DNA derived libraries, hybridization and capture was performed iteratively with probes specifically targeting V loci, 3′-UTR sequences, or J loci under standard SeqCap (Roche) conditions with xGen blocking oligos (IDT) and human Cot-1 blocking DNA (Invitrogen). Hybridization is performed at 50 C overnight. The Capture process consisting of bead incubations and washes are performed at 50 C.

For the iterative hybridization and capture process, the first J hybridization and capture is performed in completion with terminal PCR amplification with 4 steps. Following clean-up by Agencourt AMPure XP SPRI bead purification (Beckman) this product is used as input for a subsequent depletion step. For depletion, a modified and truncated SeqCap protocol is employed wherein following incubation of the hybridization mixture with M-270 streptavidin linked magnetic beads (Invitrogen), the 15 uL hybridization reaction is separated on a magnetic rack, the supernatant is recovered and diluted to 100 uL with TE buffer, followed by clean up by standard Agencourt AMPure XP SPRI bead purification (Beckman). The depletion-probe-target-beads are discarded. The purified supernatant is then used as input for a subsequent V-panel capture and hybridization as described above, but with terminal PCR amplification with 16 or amplifications steps to achieve sufficient library for sequencing.

Capture Analysis—

A custom Bash/Python/R pipeline was employed for analysis of paired read sequencing data generated by Illumina NextSeq 2500 instrument from the hybrid-capture products. First, 150 bp paired reads were merged using PEAR 0.9.6 with a 25 bp overlap parameter. This results in a single 275 bp sequence for each sequenced fragment. Next, specific V, J, and D genes within the fragment sequence were identified by aligning regions against a reference sequence database. Specifically, individual BLAST databases were created using all annotated V, D, J gene segments retrieved from the IMGT/LIGM-DB website (www.imgt.org), as these full-length gene sequences were the source of probes used to design the hybrid-capture probe panel. Individual merged reads are iteratively aligned using BLASTn with an e value cut-off of 1 to the V database, J database then D database with word size of 5 for D segment queries. Trimming of identified V or J segments in the query sequence is performed prior to subsequent alignment. From reads containing V and J sequences, we identified V/J junction position and the antigen specificity determining Complementarity Determining Region 3 (CDR3) sequences. In order to identify CDR3 sequences, the V/J junction position is extracted from the previous search data for those fragments containing both a V and J search result. 80 bp of DNA sequence flanking this junction is translated to amino acid sequence in all six open reading frames and sequences lacking stop codons are searched for invariable anchor residues using regular expressions specific for each TR class as determined by sequence alignments of polyclonal hybrid-captured data from rearranged TR polypeptides annotated by IMGT.

Results and Discussion

Methods Improvement

We experimented with alternate capture methods, using an iterative three-step hybridization and capture, first with a J panel then molecular depletion of unrearranged V-gene sequences, then subsequently with a V panel (FIG. 12). The depletion probes (V-gene and J-gene) are shown in Table D. These altered protocols improved recovery of unique CDR3 sequences when normalized to reads. When compared to a one-step V-panel capture, the one-step combined VJ-panel capture increased signal by 6.84×, the two-step J and V iterative capture increased signal by 12× (no significant difference was observed for J-V or V-J iterative order), and the three-step J-depletion-V iterative capture increased signal by 31.2× (FIG. 13).

We experimented with reducing hybridization and wash temperatures to improve recovery (FIG. 14). When 50 C to 65 C in 5 C increments were tested at each step of the hybridization and capture, 50 C yielded the highest signal and diversity.

We determined the best method for depletion (FIG. 15). We found that direct reuse of the hybridization mixture following bead-probe-target separation yielded reduced signal than setting up a new reaction following Agencourt XP bead purification of the supernatant. We also found that direct separation rather than separation of the hybridization following addition of wash buffer yielded increased signal.

We tested whether depletion should be preceded by a V or J capture (FIG. 16). We found that direct depletion of the library, followed by V or J capture yielded reduced signal compared to either V-Depletion-J or J-Depletion-V, both of which had increased, yet similar yields.

Input Source Material Comparisons

To determine whether we could characterize the TCR repertoire from both low and high signal samples, we performed a series of dilution curves for CD3+ genomic DNA (FIG. 17), PBMC genomic DNA (FIG. 18), and PBMC derived cDNA (FIG. 19). Less input actually yielded a higher amount of diversity when normalized for input and reads suggesting that high input libraries are being undersequenced or that probes are being saturated and leaving behind less preferable, but still on-target, targets. Additionally, we observed yields for the cDNA samples to be ˜100× that of genomic DNA reflecting enrichment of the TCR signal as a consequence of the high level of transcript expression of the rearranged TCR gene relative to other genes. In contrast, signal from genomic DNA is a related to the fraction of the complete genome of the target sequence and capture efficiency.

Since each sequenced sample represents only a snapshot of the TCR repertoire with the extent dependent on the amount of input material and the complexity of the source repertoire, we were interested in whether the method could assay complete VJ or CDR3 saturation of a patient. We looked at unique VJ pair recovery across multiple samples derived from a single patient blood draw (FIG. 20). Beta locus VJ saturation was achieved with fewer than ten runs. With sufficient input and sequencing depth, VJ saturation could be achieved in a single run. We also looked at CDR3 saturation across these same samples and were able to achieve approximately 50% beta locus saturation (FIG. 21). This level could be achieved with fewer samples by using cDNA libraries as input with deeper sequencing.

We looked at whether the genomic DNA and cDNA samples were recapitulating the same VJ combinations at the beta locus (FIG. 22). This was largely the case with only two discordant VJ pairs showing greater (<3% overall) change.

We looked at whether the genomic DNA and cDNA samples were recapitulating the same CDR3 sequences (FIG. 23). For the most prevalent 1000 CDR3 sequences detected from genomic DNA, their correlation with cDNA prevalences had an r squared value of 0.67. Many had similar prevalences however a large number had very low or zero prevalence values in cDNA. This is likely explained by the second group consisting of non-productive rearrangements that are encoded on the alternate chromosome and which are not expressed.

Investigation of Samples from Adoptive Cell Transfer Immunotherapy

We next applied the CapTCR-Seq methodology to samples derived from expanded Tumor Infiltrating Lymphocyte (TIL) infusion populations and PBMCs from serial blood draws from patients undergoing adoptive cell transfer immunotherapy. We wanted to track clones from the TIL culture over time to determine whether they successfully colonized the patient and the extent of their population over time (FIG. 24). Repertoire profiling reveals a polyclonal and diverse baseline repertoire before treatment, a less complex oligoclonal TIL derived culture, less complex oligoclonal repertoires following chemodepletion and transfusion of the TIL infusion, and finally restoration of a more complex polyclonal repertoire over time. When compared to the baseline, highly prevalent clones in the TIL infusion product persist over time albeit in decreasing amounts. The dominant rearrangements decrease in prevalence over time as the native repertoire is reestablished however the TIL product rearrangements persist. We can observe this persistence by graphing the individual profiles for these top nine rearrangements over time (FIG. 25). We can see that while they decrease over time, they remain higher than what was found in the apheresis sample after two years.

Comparison Between Uncaptured and Captured Tumor Samples

We wished to demonstrate the value of this method for interrogating existing cDNA RNA-Seq libraries (FIG. 26). To do this, Illumina cDNA sequencing libraries were generated from FFPE-derived total RNA and subjected to sequencing followed by analysis using the TCR annotation pipeline to identify unique TCR CDR3 sequences (bulk unique CDR3). Residual library then underwent CapTCR-Seq to identify unique TCR CDR3 sequences (capture unique CDR3). The CapTCR-Seq method yielded a greatly increased number of unique CDR3 sequences (mean: 466 fold, median: 353 fold). When normalized to number of total reads sequenced, we observed a 15 fold increase in signal per read sequenced (mean:15.2, median:14.5, n=41).

Investigation of Tumor Repertoires from Different Cancer Types

We next wanted to characterize tumor repertoires and investigate highly prevalent TIL clones in the blood repertoire before and during anti-PDL1 immunotherapy treatment. We selected five patients, each with a different tumor type: Patient A: Head and neck; Patient B: Breast; Patient C: Ovarian; Patient D: Melanoma; Patient E: Cervical. Each patient had three sample types: Tumor tissue (extracted DNA and RNA), pre-treatment blood (extracted PBMC DNA, PBMC RNA, and plasma cfDNA), on-treatment blood (extracted plasma cfDNA).

We first queried the extent of the TCR signal in the tumor samples in terms of infiltration and clonality. TCR signal is defined as the total number of counts of fragments containing both a V and J gene region (non-unique, reads normalized) while diversity is defined as the total number of unique CDR3 sequences detected (unique, reads normalized). Overall, diversity increased with signal (FIG. 27). cfDNA samples had the lowest signal, genomic DNA samples had intermediate signal, while cDNA samples had the highest signal. Blood sample signal and diversity is similar for all five patients, however tumor signal and diversity varied. Two patients had ten-fold higher TCR signal and diversity in their tumors likely reflecting increased infiltration of immune cells (FIG. 28).

Next we assessed the clonality of the tumor sample TIL repertoire. Tumors with clonal infiltration have a larger than expected population of one or more VJ rearrangements, the population of which are significantly greater than the next most prevalent clone. Patient A appears to have a large alpha rearrangement population in its tumor compared to baseline blood, while the most prevalent beta rearrangement is only slightly enriched (FIG. 29-30). The tumor sample for patient B showed both greatly enriched top alpha and beta VJ rearrangements compared to baseline blood (FIG. 31-32). The tumor sample for patient C showed both greatly enriched top alpha and beta VJ rearrangements compared to baseline blood (FIG. 33-34). The tumor sample for patient D showed both greatly enriched top alpha (2) and beta VJ (1) rearrangements compared to baseline blood (FIG. 35-36). The tumor sample for patient E showed only a slightly enriched top beta VJ rearrangement compared to baseline blood (FIG. 37-38).

Next we assessed how the most prevalent tumor VJ rearrangements differed in terms of prevalence across the other patient samples (FIGS. 39-43). In general, prevalent TIL clones were not prevalent in the blood repertoire demonstrating clonal expansion within the tumor or selective infiltration. However, for a number of the most prevalent TIL clones, we saw very high levels within the plasma samples suggesting that while these clones are actively undergoing cell death. In combination with their high tumor infiltration, this suggests that these are anti-tumor T-cells undergoing active expansion, anti-tumor cytotoxicity and turnover.

Example 4

We performed similar experiments relating to B-cells. Our design targets more than 500 V-regions and 50 J-regions within the IGH, IGK and IGL loci annotated in the IMmunoGeneTics database. This accounts for all known Ig alleles while maximizing depth of coverage in selected regions. A blast-based informatics pipeline calls V(D)J recombinations and an algorithm combining information from large-insert and soft-clipped reads are used to predict candidate rearrangements which are manually verified in Integrated Genome Viewer.

Candidate V(D)J rearrangements and translocations detected through this approach have been validated in three well-characterized cell-lines with publically available whole genome data; an additional 67 MM cell lines have been annotated for V(D)J rearrangements and translocations into IGH, IGL and IGK genes. The limit of detection was established with a cell-line dilution series. We were also able to translate these techniques to cell-free DNA. These methods are applicable to the detection of MRD in mature B-cell malignancies and immunoglobulin repertoire profiling in a many clinical scenarios including cellular immunotherapy and therapeutics with immunomodulatory effects. V(D)J and complex rearrangement annotations in 70 MM cell-lines are highly relevant in further in-vitro studies.

The B-cell V-gene and J-gene capture probes used are shown in Tables B1 and B2 respectively.

Although preferred embodiments of the invention have been described herein, it will be understood by those skilled in the art that variations may be made thereto without departing from the spirit of the invention or the scope of the appended claims. All documents disclosed herein, including those in the following reference list, are incorporated by reference.

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List of Abbreviations ATCC American Type Culture Collection (Biorepository) AUC Area-under-the-curve bp basepair BWA Burrows-Wheeler Alignment algorithm CIHI Canadian Institutes for Health Information D T-cell receptor “diversity” type gene DAD Discharge Abstracts Database (CIHI database) DSMZ Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (German Collection of Microorganisms and Cell Cultures) FDR False-Discovery Rare FFPE Formalin-fixed paraffin-embedded ICD-10 International classification of disease, version 10 IG Immunoglobulin IMGT The International standard source for ImMunoGeneTics sequences & metadata J T-cell receptor gene “join” type gene kb kilobase LGL Large-Granular-Lymphocyte (Leukemia/Lymphoma) NGS Next-generation sequencing (technology) NMF Non-negative Matrix Factorization NTRA Novel NGS-based T-cell receptor gene re-arrangement assay PEAR Paired-end rEAd mergeR PTCL Peripheral T-cell lymphoma ROC Receiver-Operating Characteristic (Curve) SAM Sequence Alignment Map SEER Surveillance, epidemiology, and end results program (the primary US source of Cancer Statistics) SWA Smith-Waterman Alignment (algorithm) TGH Toronto General Hospital TLPD T-cell lymphoproliferative disorder TR T-cell receptor TRA T-cell receptor alpha gene TRB T-cell receptor beta gene TRD T-cell receptor delta gene TRG T-cell receptor gamma gene TRGR T-cell receptor gene re-arrangement V T-cell receptor “variable” type gene WHO World Health Organization

TABLE 2.1 SEQ ID NO Name Sequence SEQ ID NO: 873 TRAV1-1*01-5′ ggacaaagccttgagcagccctctgaagtgacagctgtggaaggagccattgtccagataaactgcacgtaccagacatctgggttttatgggctgtcct SEQ ID NO: 874 TRAV101*01-3′ gtttttcttcattccttagtcgctctgatagttatggttacctccttctacaggagctccagatgaaagactctgcctcttacttctgcgctgtgagaga SEQ ID NO: 875 TRAV1-1*02-5′ ggacaaagccttgagcagccctctgaagtgacagctgtggaaggagccattgtccagataaactgcacgtaccagacatctgggttttatgggctgtcct SEQ ID NO: 876 TRAV1-1*02-3′ caggtcgtttttccttcattccttagtcgctctgatagttatggttacctccttctacaggagctccagatgaaagactctgcctcttacttctgcgctgt SEQ ID NO: 877 TRAV1-2*01-5′ ggacaaaacattgaccagcccactgagatgacagctacggaaggtgccattgtccagatcaactgcacgtaccagacatctgggttcaacgggctgttct SEQ ID NO: 878 TRAV1-2*01-3′ gtttttccttcattccttagtcggtctaaagggtacagttacctccttttgaaggagctccagatgaaagactctgcctcttacctctgtgctgtgagaga SEQ ID NO: 879 TRAV1-2*02-5′ ggacaaaacattgaccagcccactgagatgacagctacggaaggtgccattgtccagatcaactgcacgtaccagacatctgggttcaacgggctgttct SEQ ID NO: 880 TRAV1-2*02-3′ catctgggttcaacgggctgttctggtaccagcaacatgctggcgaagcacccacatttctgtcttacaatgttctggatggtctggaggagaaaggtcg SEQ ID NO: 881 TRAV10*01-5′ aaaaaccaagtggagcagagtcctcagtccctgatcatcctggagggaaagaactgcactcttcaatgcaattatacagtgagccccttcagcaacttaa SEQ ID NO: 882 TRAV10*01-3′ agatatacagcaactctggatgcagacacaaagcaaagctctctgcacatcacagcctcccagctcagcgattcagcctcctacatctgtgtggtgagcg SEQ ID NO: 883 TRAV11*01-5′ ctacatacactggagcagagtccttcattcctgaatattcaggagggaatgcatgccgttcttaattgtacttatcaggagagaacactcttcaatttct SEQ ID NO: 884 TRAV11*01-5′ caaatattttaaagaactgcttggaaagaaaaattttatagtgtttggaatatcgcagcctctcatctgggagattcagccacctacttctgtgctttg SEQ ID NO: 885 TRAV12-1*01-5′ cggaaggaggtggagcaggatcctggacccttcaatgttccagagggagccactgtcgctttcaactgtacttacagcaacagtgcttctcagtctttct SEQ ID NO: 886 TRAV12-1*01-3′ aggtttacagcacagctcaatagagccagccagtatatttccctgctcatcagagactccaagctcagtgattcagccacctacctctgtgtggtgaaca SEQ ID NO: 887 TRAV12-1*02-5′ cggaaggaggtggagcaggatcctggacccttcaatgttccagagggagccactgtcgctttcaactgtacttacagcaacagtgcttctcagtctttct SEQ ID NO: 888 TRAV12-1*02-3′ acagcacacgtcaatagagccagccagtatatttccctgctcatcagagactccaagctcagtgattcagccacctacctctgtgtggtgaacattcgcc SEQ ID NO: 889 TRAV12-2*01-5′ cagaaggaggtggagcagaattctggacccctcagtgttccagagggagccattgcctctctcaactgcacttacagtgaccgaggttcccagtccttct SEQ ID NO: 890 TRAV12-2*01-3′ aggttacagcacagctcaataaagccagccagtatgtttctctgctcatcagagactcccagcccagtgattcagccacctacctctgtgccgtgaaca SEQ ID NO: 891 TRAV12-2*02-5′ cagaaggaggtggagcagaattctggacccctcagtgttccagagggagccattgcctctctcaactgcacttacagtgaccgaggttcccagtccttct SEQ ID NO: 892 TRAV12-2*02-3′ gtttacagcacagctcaataaagccagccagtatgtttctctgctcatcagagactcccagcccagtgattcagccacctacctctgtgccgtgtaccac SEQ ID NO: 893 TARV12-2*03-5′ ggacccctcagtgttccagagggagccattgcctctctcaactgcacttacagtgaccgagtttcccagtccttcttctggtacagacaatattctggga SEQ ID NO: 894 TRAV12-2*03-3′ aaggtttacagcacagctcaataaagccagccagtatgtttctctgctcatcagagactcccagcccagtgattcagccacctacctctgtgccgtgaac SEQ ID NO: 895 TRAV12-3*01-5′ cagaaggaggtggagcaggatcctggaccactcagtgttccagagggagccattgtttctctcaactgcacttacagcaacagtgcttttcaatacttca SEQ ID NO: 896 TRAV12-3*01-3′ aggtttacagcacaggtcgataaatccagcaagtatatctccttgttcatccagagactcacagcccagtgattcagccacctacctctgtgcaatgagcg SEQ ID NO: 897 TRAV12-3*02-5′ cagaaggaggtggagcaggatcctggaccactcagtgttccagagggagccattgtttctctcaactgcacttacagcaacagtgcttttcaatacttca SEQ ID NO: 898 TRAV12-3*02-3′ aggtttacagcacaggtcgataaatccagcaagtatatctccttgttcatcagagactcacagcccagtgattcagccacctacctctgtgcaatgagcg SEQ ID NO: 899 TRAV13-1*02-5′ ggagagaatgtggagcagcatccttcaaccctgagtgtccaggagggagacagcgctgttatcaagtgtacttattcagacagtgcctcaaactacttcc SEQ ID NO: 900 TRAV13-1*01-3′ cgaattgctgttacattgaacaagacagccaaacatttctccctgcacatcacagagacccaacctgaagactcggctgtctacttctgtgcagcaagta SEQ ID NO: 901 TRAV13-1*02-5′ ggagagaatgtggagcagcatccttcaaccctgagtgtccaggagggagacagcgctgttatcaagtgtacttattcagacagtgcctcaaactacttcc SEQ ID NO: 902 TRAV13-1*02-3′ tgttacattgaacaagacagccaaacatttctccctgcacatcacagagacccaacctgaagactcggctgtctacttctgtgcagcaagtaggaaggac SEQ ID NO: 903 TRAV13-1*03-5′ ggagagaatgtggagcagcatccttcaaccctgagtgtccaggagggagacagcgctggttatcaagtgtacttattcagacagtgcctcaaactacttcc SEQ ID NO: 904 TRAV13-1*03-3′ gcttattatagacattcgttcaaatgtgggcgaaaagaaagaccaacgaattgctgttacattgaacaagacagccaaacatttctccctgcagatcaca SEQ ID NO: 905 TRAV13-2*01-5′ ggagagagtgtggggctgcatcttcctaccctgagtgtccaggagggtgataactctattatcaactgtgcttattcaaacagcgcctcagactacttca SEQ ID NO: 906 TRAV13-2*01-3′ agagtcaccgttttattgaataagacagtgaaacatctctctctgcaaattgcagctactcaacctggagactcagctgtctacttttgtgcagagaata SEQ ID NO: 907 TRAV13-2*02-5′ ggagagagtgtggggctgcatcttcctaccctgagtgtccaggagggtgacaactctattatcaacztgtgcttattcaaacagcgcctcagactacttca SEQ ID NO: 908 TRAV13-2*02-3′ caaagagtcaccgttttattgaataagacagtgaaacatctctctctgcaaattgcagctactcaacctggagactcagctgtctacttttgtgcagaga SEQ ID NO: 909 TRAV14/DV4*01- gcccagaagataactcaaacccaaccaggaatgttcgtgcaggaaaaggaggctgtgactctggactgcacatatgacaccagtgatccaagttatggtc 5′ SEQ ID NO: 910 TRAV14/DV4*01- actcattgaatttccagaaggcaagaaaatccgccaaccttgtcatctccgcttcacaactgggggactcagcaatgtacttctgtgccaatgagagaggg 3′ SEQ ID NO: 911 TRAV14/DV4*02- gcccagaagataactcaaacccaaccaggaatgttcgtgcaggaaaaggaggctgtgactctggactgcacatatgacaccagtgatcaaagttatggtc 5′ SEQ ID NO: 912 TRAV14/DV4*02- actcattgaatttccagaaggcaagaaaatccgccaaccttgtcatctccgcttcacaactgggggactcagcaatgtatttctgtgcaatgagagaggg 3′ SEQ ID NO: 913 TRAV14/DV4*03- gcccagaagataactcaaacccaaccaggaatgttcgtgcaggaaaaggaggctgtgactctggactgcacatatgacaccagtgatccaagttatggtc 5′ SEQ ID NO: 914 TRAV14/DV4*03 aggtcgctactcattgaatttccagaaggcaagaaaatccgccaaccttgtcatctccgcttcacaactgggggactcagcaatgtatttctgtgcaatg 3′ SEQ ID NO: 915 TRAV14/DV4*04- cagaagataactcaaacccaaccaggaatgttcgtgcaggaaaaggaggctgtgactctggactgcacatatgacaccagtgatcaaagttatggtctct 5′ SEQ ID NO: 916 TRAV14/DR4*04- gcaacagaaggtcgctactcattgaatttccagaaggcaagaaaatccgccaaccttgtcatctccgcttcacaactgggggactcagcaatgtacttct 3′ SEQ ID NO: 917 TRAV15*01-5′ ctccatattctggagtagagtccttcattcattcctgagtatccgggagggaatgcacaacattcttaattgcacttatgaggagagaacgttctcttaa SEQ ID NO: 918 TRAV15*01-3′ acattttaaagaagcgcttggaaaagagaagttttatagtgttttgaatatgctggtctctcatcctggagattcaggcacctacttctgtgctttgaag SEQ ID NO: 919 TRAV16*01-T′ gcccagagagtgactcagcccgagaaagctcctctctgtctttaaaggggccccagtggagctgaagtgcaactattcctattctgggagtcctgaactct SEQ ID NO: 920 TRAV16*01-3′ gcttcactgctgaccttaacaaaggcgagacatcttttcacctgaagaaaccatttgctcaagaggaagactcagccatgtattactgtgctctaagtgg SEQ ID NO: 921 TRAV17*01-5′ agtcaacagggagaagaggatcctcaggccttgagcatccaggagggtgaaaatgccaccatgaactgcagttacaaaactagtataaacaatttacagt SEQ ID NO: 922 TRAV17*-1-3′ agattaagagtcacgcttgacacttccaagaaaagcagttccttgttgatcacggcttcccgggcagcagacactgcttcttacttctgtgctacggacg SEQ ID NO: 923 TRAV18*01-5′ ggagactcggttacccagacagaaggcccagttaccctccctgagagggcagctctgacattaaactgcacttatcagtccagctattcaacttttctat SEQ ID NO: 924 TRAV18*01-3′ gttttcaggccagtcctatcaagagtgacagttccttccacctggagaagccctcggtgcagctgtcggactctgccgtgtactactgcgctctgagaga SEQ ID NO: 925 TRAV19*01-5′ gctcagaaggtaactcaagcgcagactgaaatttctgtggtggagaaggaggatgtgaccttggactgtgtgtatgaaacccgtgatactacttattact SEQ ID NO: 926 TRAV19*01-3′ attcttggaacttccagaaatccaccagttccttcaacttcaccatcacagcctcacaagtcgtggactcagcagtatacttctgtgctctgagtgaggc SEQ ID NO: 927 TRAV2*01-5′ aaggaccaagtgtttcagccttccacagtggcatcttcagagggagctgtggtggaaatcttctgtaatcactctgtgtccaatgcttacaacttcttct SEQ ID NO: 928 TRAV2*01-3′ agggacgatacaacatgacctatgaacggttctcttcatcgctgctcatcctccaggtgcgggaggcagatgctgctgtttactactgtgctgtggagga SEQ ID NO: 929 TRAV2*02-5′ aaggaccaagtgtttcagccttccacagtggcatcttcagagggagctgtggtggaaatcttctgtaatcactctgtgtccaatgcttacaacttcttct SEQ ID NO: 930 TRAV2*02-3′ gggacgatacaacatgacctatgaacggttctcttcatcgctgctcatcctccaggtgcgggaggcagatgctgctgtttactactgtgctgtggcctgg SEQ ID NO: 931 TRAV20*01-5′ gaagaccaggtgacgcagagtcccgaggccctgagactccaggagggagagagtagcagtcttaactgcagttacacagtcagcggtttaagagggctgt SEQ ID NO: 932 TRAV20*01-3′ aaagaaaggctaaaagccacattaacaaagaaggaaagctttctgcacatcacagcccctaaacctgaagactcagccacttatctctgtgctgtgcagg SEQ ID NO: 933 TRAV20*02-5′ gaagaccaggtgacgcagagtcccgaggccctgagactccaggagggagagagtagcagtctcaactgcagttacacagtcagcggtttaagagggctgt SEQ ID NO: 934 TRAV20*02-3′ aaaggagaaagaaaggctaaaagccacattaacaaagaaggaaagctttctgcacatcacagcccctaaacctgaagactcagccacttatctctgtgct SEQ ID NO: 935 TRAV20*03-5′ gaagaccaggtgacgcagagtcccgaggccctgagactccaggagggagagagtcgcagtctcaactgcagttacacagtcagcggtttaagagggctgt SEQ ID NO: 936 TRAV20*03-3′ agaaaaggagaaagaaaggctaaaagccacattaacaagaaggaaagctttctgcacatcacagcccctaaacctgaagactcagccacttatctctgt SEQ ID NO: 937 TRAV20*04-5′ gaagaccaggtgacgcagagtcccgaggccctgagactccaggagggagagagtagcagtctcaactgcagttgcacagtcagcggtttaagagggctgt SEQ ID NO: 938 TRAV20*04-3′ aaaggagaaagaaaggctaaaagccacattaacaaagaaggaaagctttctgcacatcacagcccctaaacctgaagactcagccacttatctctgtgct SEQ ID NO: 939 TRAV21*01-5′ aaacaggaggtgacgcagattcctgcagctctgagtgtcccagaaggagaaaacttggttctcaactgcagtttcactgatagcgctatttacaacctcc SEQ ID NO: 940 TRAV21*01-3′ aagacttaatgcctcgctggataaatcatcaggacgtagtactttatacattgcagcttctcagcctggtgactcagccacctacctctgtgctgtgagg SEQ ID NO: 941 TRAV21*02-5′ aaacaggaggtgacacagattcctgcagctctgagtgtcccagaaggagaaaacttggttctcaactgcagtttcactgatagcgctattacaacctcc SEQ ID NO: 942 TRAV21*02-3′ aagtggaagacttaatgcctcgctggataaatcatcaggacgtagtactttatacattgcagcttctcagcctggtgactcagccacctacctctgtgct SEQ ID NO: 943 TRAV22*01-5′ ggaatacaagtggagcagagtcctccagacctgattctccaggagggagccaattccacgctgcggtgcaatttttctgactctgtgaacaatttgcagt SEQ ID NO: 944 TRAV22*01-3′ agattaagcgccacgactgtcgctacggaacgctacagcttattgtacatttcctcttcccagaccacagactcaggcgtttatttctgtgctgtggagc SEQ ID NO: 945 TRAV23/DV6*01- cagcagcaggtgaaacaaagtcctcaatcttgatagtccagaaaggagggatttcaattataaactgtgcttatgagaacactgcgtttgactactttc 5′ SEQ ID NO: 946 TRAV23/DV6*01- agattcacaatctccttcaataaaagtgccaagcagttctcattgcatatcatggattcccagcctggagactcagccacctacttctgtgcagcaagta 3′ SEQ ID NO: 947 TRAV23/DV6*02- cagcagcaggtgaaacaaagtcctcaatctttgatagtccagaaaggagggattccaattataaactgtgcttatgagaacactgcgtttgactactttc 5′ SEQ ID NO: 948 TRAV23/DV6*02- agattcacaatctccttcaataaaagtgccaagcagttctcattgcatatcatggattcccagcctggagactcagccacctacttctgtgcagcaagcg 3′ SEQ ID NO: 949 TRAV23/DV6*03- cagcagcaggtgaaacaaagtcctcaatctttgatagtccagaaaggagggatttcaattataaactgtgcttatgagaacactgcgtttgactactttc 5′ SEQ ID NO: 950 TRAV23/DV6*03- agattcacaatctccttcaataaaagtgccaagcagttctcattgcatatcatggattcccagcctggagactcagccacctacttctgtgcagcaagca 3′ SEQ ID NO: 951 TRAV23/DV6*04- cagcaggtgaaacaaagtcctcaatctttgatagtccagaaaggagggatttcaattataaactgtgcttatgagaacactgcgtttgactactttccat 5′ SEQ ID NO: 952 TRAV23/DV6*04- gaaagaaggaagattcacaatctccttcaataaaagtgccaagcagttctcattgcatatcatggattcccagcctggagactcagccacctacttctgt 3′ SEQ ID NO: 953 TRAV24*01-5′ aggacgaataagtgccactcttaataccaaggagggttacagctatttgtacatcaaaggatcccagcctgaagactcagccacatacctctgtgccttt SEQ ID NO: 954 TRAV24*01-3′ ggacgaataagtgccactcttaataccaaggagggttacagctatttgtacatcaaaggatcccagcctgaagactcagccacatacctctgtgccttta SEQ ID NO: 955 TRAV24*02-5′ atactgaacgtggaacaaggtcctcagtcactgcatgttcaggagggagacagcaccaatttcacctgcagcttcccttccagcaatttttatgccttac SEQ ID NO: 956 TRAV24*02-3′ ggacgaataagtgccactcttaataccaaggagggttacagctatttgtacatcaaaggatcccagcctgaagattcagccacatacctctgtgccttta SEQ ID NO: 957 TRAV25*01-5′ ggacaacaggtaatgcaaattcctcagtaccagcatgtacaagaaggagaggacttcaccacgtactgcaattcctcaactactttaagcaatatacagt SEQ ID NO: 958 TRAV25*01-3′ gaaaagactgacatttcagtttggagaagcaaaaaagaacagctccctgcacatcacagccacccagactacagatgtaggaacctacttctgtgcaggg SEQ ID NO: 959 TRAV26-1*01-5′ gatgctaagaccacccagcccccctccatggattgcgctgaaggaagagctgcaaacctgccttgtaatcactctaccatcagtggaaatgagtatgtgt SEQ ID NO: 960 TRAV26-1*01-3′ gcctctctgatcatcacagaagacagaaagtccagcaccttgatcctgccccacgctacgctgagagacactgctgtgtactattgcatcgtcagagtcg SEQ ID NO: 961 TRAV26-1*02-5′ gatgctaagaccacccagcccacctccatggattgcgctgaaggaagagctgcaaacctgccttgtaatcactctaccatcagtggaaatgagtatgtgt SEQ ID NO: 962 TRAV26-1*02-3′ ctctgatcatcacagaagacagaaagtccagcaccttgatcctgccccacgctacgctgagagacactgctgtgtactattgcatcgtcagagattgggt SEQ ID NO: 963 TRAV26-1*03-5′ gatgctaagaccacccagcccccctccatggattgcgctgaaggaagagctgcaaacctgccttgtaatcactctaccatcagtggaaatgagtatgtgt SEQ ID NO: 964 TRAV26-1*03-3′ caatgaaatggcctctctgatcatcacagaagacagaaagtccagcaccttgatcctgccccacgctacgctgagagacactgctgtgtactattgcatc SEQ ID NO: 965 TRAV26-2*01-5′ gatgctaagaccacagccaaattcaatggagagtaacgaagaagagcctgttcacttgccttgtaaccactccacaatcagtggaactgattacatac SEQ ID NO: 966 TRAV26-2*01-3′ ggcctctctggcaatcgctgaagacagaaagtccagtaccttgatcctgcaccgtgctaccttgagagatgctgctgtgtactactgcatcctgagagac SEQ ID NO: 967 TRAV26-2*02-5′ gatgctaagaccacacagccaaattcaatggagagtaacgaagaagagcctgttcacttgccttgtaaccactccacaatcagtggaactgattacatac SEQ ID NO: 968 TRAV26-2*02-3′ ccctcccagggtccagagtacgtgattcatggtcttacaagcaatgtgaacaacagaatggcctgtgtggcaatcgctgaagacagaaagtccagtacct SEQ ID NO: 969 TRAV27*01-5′ acccagctgctggagcagagccctcagtttctaagcatccaagagggagaaaatctcactgtgtactgcaactcctcaagtgttttttccagcttacaat SEQ ID NO: 970 TRAV27*01-3′ aagagactaacctttcagtttggtgatgcaagaaaggacagttctctccacatcactgcagcccagcctggtgatacaggcctctacctctgtgcaggag SEQ ID NO: 971 TRAV27*02-5′ acccagctgctggagcagagccctcagtttctaagcatccaagagggagaaaatctcactgtgtactgcaactcctcaagtgtttttccagcttacaat SEQ ID NO: 972 TRAV27*02-3′ tgaagagactaacctttcagtttggtgatgcaagaaaggacagttctctccacatcactgcggcccagcctggtgatacaggccactacctctgtcagg SEQ ID NO: 973 TRAV27*03-5 acccagctgctggagcagagccctcagtttctaagcatccaagagggagaaaattcactgtgtactgcaactcctcaagtgttttttccagcttacat SEQ ID NO: 974 TRAV27*03-3′ gctgaagagactaacctttcagtttggtgatgcaagaaaggacagttctctccacatcactgcagcccagactggtgatacaggcctctacctctgtgca SEQ ID NO: 975 TRAV28*01-5′ aaagtggagcagagtcctcaggtcctgatcctccaagagggaagaaattcattcctggtgtgcagttgttctatttacatgatccgtgtgcagtggtttc SEQ ID NO: 976 TRAV28*01-3′ gaagactaaaatccgcagtcaaagctgaggaactttatggccacctatacatcagattcccagcctgaggactcagctatttacttctgtgctgtgggga SEQ ID NO: 977 TRAV29/DV5*01- gaccagcaagttaagcaaaattcaccatccctgagcgtccaggaaggaagaatttctattctgaactgtgactatactaacagcatgtttgattatttcc 5′ SEQ ID NO: 978 TRAV29/DV5*01- agattcactgtcttcttaaacaaaagtgccaagcacctctctctgcacattgtgccctcccagcctggagactctgcagtgtacttctgcagcaagcg 3′ SEQ ID NO: 979 TRAV29/DV5*02- gaccagcaagttaagcaaaattcaccatccctgagcgtccaggaaggaagaatttctattctgaactgtgactatactaacagcatgtttgattatttcc 5′ SEQ ID NO: 980 TRAV29/DV5*02- aagattcactgttttcttaaacaaaagtgccaagcatctctctctcgacattgtgccctcccagcctggagactctgcagtgtacttctgtgcagcaagc 3′ SEQ ID NO: 981 TRAV29/DV5*03- gaccagcaagttaagcaaaattcaccatccctgagcgtccaggaaggaagaatttctattctgaactgtgactatactaacagcatgtttgattatttcc 5′ SEQ ID NO: 982 TRAV29/DV5*03- agattcactgttttcttaaacaaaagtgccaagcacctctctctgcacattgtgccctcccagcctggagactctgcagtgtacttctgtgcagcaagcg 3′ SEQ ID NO: 983 TRAV3*01-5′ gctcagtcagtggctcagccggaagatcaggtcaacgttgctgaagggaatcctctgactgtgaaatgcacctattcagtctctggaaacccttatcttt SEQ ID NO: 984 TRAV3*01-3′ tttgaagctgaatttaacaagagccaaacctccttccacctgaagaaaccatctgcccttgtgagcgactccgctttgtacttctgtgctgtgagagaca SEQ ID NO: 985 TRAV3*02-5′ gctcagtcagtggctcagcggaagatcaggtcaacgttgctgaagggaatcctctgactgtgaaatgcacctattcagtctctggaaacccttatctttt SEQ ID NO: 986 TRAV3*02-3′ ctttgaagctgaatttaacaagagccaaacctccttccacctgaagaaaccatctgcccttgtgagcgactccgctttgtacttctgtgctgtgagaccc SEQ ID NO: 987 TRAV30*01-5′ caacaaccagtgcagagtcctcaagccgtgatcctccgagaaggggaagatgctgtcatcaactgcagttcctccaaggctttatattctgtacactggt SEQ ID NO: 988 TRAV30*01-3′ aaaatatctgcttcatttaatgaaaaaaagcagcaaagctccctgtaccttacggcctcccagctcagttactcaggaacctacttctgcggcacagaga SEQ ID NO: 989 TRAV30*02-5′ caacaaccagtgcagagtcctcaagccgtgatcctccgagaaggggaagatgctgtcaccaactgcagttcctccaaggctttatattctgtacactggt SEQ ID NO: 990 TRAV30*02-3′ tcgtgaaaaaatatctgcttcatttaatgaaaaaaagcagcaaagctccctgtaccttacggcctcccagctcagttactcaggaacctacttctgcggg SEQ ID NO: 991 TRAV30*03-5′ caacaaccagtgcagagtcctcaagccgtgatcctccgagaaggggaagatgctgtcatcaactgcagttcctccaaggctttatattctgtacactggt SEQ ID NO: 992 TRAV30*03-3′ tcatgaaaaaatatctgcttcatttaatgaaaaaaagcggcaaagctccctgtaccttacggcctcccagctcagttactcaggaacctacttctgcggc SEQ ID NO: 993 TRAV30*04-5′ caacaaccagtgcagagtcctcaagccgtgatcctccgagaaggggaagatgctgtcatcaactgcagttcctccaaggctttatattctgtacactggt SEQ ID NO: 994 TRAV30*04-3′ tcctgatgatattactgaagggtggagaacagaagcgtcatgaaaaaatatctgcttcatttaatgaaaaaaagcagcaaagctccctgtaccttacggc SEQ ID NO: 995 TRAV31*01-5′ cagagggtcattcaatcccaaccagcaatatctacgtaggagggtgagaccgtgaaactggactgtgcatacaaaactaatattgtatattacatattgt SEQ ID NO: 996 TRAV31*01-3′ tattctgtgagcttccagaaaacaactaaaactattcagcttatcatatcatcatcacagccagaagacctgcaacatatttctgttgtctcaaagagcc SEQ ID NO: 997 TRAV32*01-5′ aaggatgtgatacagagttattcaaatctaaatgtctaggagagagaatggccgttattaatgacagttatacagatggagctttgaattatttctgtt SEQ ID NO: 998 TRAV32*01-3′ aggctcactgtactgttgaataaaaatgctaaacatgtctccctgcatattacagccacccaaccaggagactcattcctgtacttctgtgcagtgagaa SEQ ID NO: 999 TRAV33*01-5′ gctcagaaagtaacccaagttcagaccacagtaactaggcagaaaggagtagctgtgaccttggactgcatgtttgaaaccagatagaattcgtacactt SEQ ID NO: 1000 TRAV33*01-3′ gcaaagcctgtgaactttgaaaaaaagaaaaagttcatcaacctcaccatcaattccttaaaactgactcagccaagtacttctgtgctctcaggaatcc SEQ ID NO: 1001 TRAV34*01-5′ agccaagaactggagcagagtcctcagtccttgatcgtccaagagggaaagaatctcaccataaactgcacgtcatcaaagacgttatatggcttatact SEQ ID NO: 1002 TRAV34*01-3′ aagataactgccaagttggatgagaaaaagcagcaaagttccctgcatatcacagcctcccagcccagccatgcaggcatctacctctgtggagcagaca SEQ ID NO: 1003 TRAV35*01-5′ ggtcaacagctgaatcagagtcctcaatctatgtttatccaggaaggagaagatgtctccatgaactgcacttcttcaagcatatttaacacctggctat SEQ ID NO: 1004 TRAV35*01-3′ aagactgactgctcagtttggtataaccagaaaggacagcttcctgaatatctcagcatccatacctagtgatgtaggcatctacttctgtgctgggcag SEQ ID NO: 1005 TRAV35*02-5′ ggtcaacagctgaatcagagtccctcaatctatgtttatccaggaaggagaagatgtctccatgaactgcacttcttcaagcatatttaacacctggctat SEQ ID NO: 1006 TRAV35*02-3′ aaatggaagactgactgctcagtttggtataaccagaaaggacagcttcctgaatatctcagcatccatacctagtgatgtaggcatctacttctgtgct SEQ ID NO: 1007 TRAV36/DV7*01- gaagacaaggtggtacaaagccctctatctctggttgtccacgagggagacaccgtaactctcaattgcagttatgaagtgactaactttcgaagcctac 5′ SEQ ID NO: 1008 TRAV36/DV7*01- agactaagtagcatattagataagaaagaactttccagcatcctgaacatcacagccacccagaccggagactcggccatctacctctgtgctgtggagg 3′ SEQ ID NO: 1009 TRAV36/DV7*02- gaagacaaggtggtacaaagccctcaatctctggttgtccacgagggagacattgtaactctcaattgcagttatgaaatgactaactttcgaagcctac 5′ SEQ ID NO: 1010 TRAV36/DV7*02- ggaagactaagtagcatattagataagaaagaacttttcagcatcctgaacatcacagccacccagaccggagactcggccgtctacctctgtgctgtgg 3′ SEQ ID NO: 1011 TRAV36/DV7*03- gaagacaaggtggtacaaagccctctatctctggttgtccacgagggagacactgtaactcccaattgcagttatgaagtgactaactttcgaagcctac 5′ SEQ ID NO: 1012 TRAV36/DV7*03- gtcaggaagactaagtagcatattagataagaagaacttttcagcatcctgaacatcacagccacccagaccggagactcggccgtctacctctgtgct 3′ SEQ ID NO: 1013 TRAV36/DV7*04- gaagacaaggtggtacaaagccctctatctctggttgtccacgagggagacactgtaactctcaattgcagttatgaagtgactaactttcgaagcctac 5′ SEQ ID NO: 1014 TRAV36/DV7*04- tcaggaagactaagtagcatattagataagaaagaacttttcagcatcctgaacatcacagccacccagaccggagactcggccgtctacctctgtgctg 3′ SEQ ID NO: 1015 TRAV37*01-5′ caactgccagtggaacagaatgctccttccctgaaagtcaaggaaggtgacagcgtcacactgaactgcagttacagagacagcccttcagatttcttca SEQ ID NO: 1016 TRAV37*01-3′ agattcacagccaggcttaaaaaaggagaccagcacatttccctgcacatacaggattcccagctccatgactcaaccacattcttctgcgcagcaagca SEQ ID NO: 1017 TRAV38-1*01-5′ gcccagacagtcactcagtctcaaccagagatgtctgtgcaggaggcagagactgtgaccctgagttgcacatatgacaccagtgagaataattattatt SEQ ID NO: 1018 TRAV38-1*01-3′ tctctgtgaacttccagaaagcagccaaatccttcagtctcaagatctcagactcacagctgggggacactgcgatgtatttctgtgctttcatgaagca SEQ ID NO: 1019 TRAV38-1*02-5′ gcccagacagtcactcagtctcaaccagagatgtctgtgcaggaggcagagactgtgaccctgagttgcacatatgacaccagtgagaatgattattatt SEQ ID NO: 1020 TRAV38-1*02-3′ gagaatcgtttctctgtgaacttccagaaagcagccaaatccttcagtctcaagatctcagactacagctgggggacactgcgatgtatttctgtgctt SEQ ID NO: 1021 TRAV38-1*03-5′ gcccagacagtcactcagtctcaaccagagatgtctgtgcaggaggcagagactgtgaccctgagttgcacatatgacactagtgagagtaattattatt SEQ ID NO: 1022 TRAV38-1*03-3′ aatcgtttctctgtgaacttccagaaagcagccaaatccttcagtctcaagatctcagactcacagctgggggacactgcgatgtatttctgtgctttca SEQ ID NO: 1023 TRAV38-1*04-5′ gcccagacagtcactcagtcccagccagagatgtctgtgcaggaggcagagactgtgaccctgagttgcacatatgacaccagtgagaataattattatt SEQ ID NO: 1024 TRAV38-1*04-3′ ggagaatcgtttctctgtgaacttccagaaagcagccaaatccttcagtctcaagatctcagactcacagctgggggacactgcgatgtatttctgtgca SEQ ID NO: 1025 TRAV38- gctcagacagtcactcagtctcaaccagagatgtctgtgcaggaggcagagaccgtgaccctgagctgcacatatgacaccagtgagagtgattattatt 2/DV8*01-5′ SEQ ID NO: 1026 TRAV38- ttctctgtgaacttccagaaagcagccaaatccttcagtctcaagatctcagactcacagctgggggatgccgcgatgtatttctgtgcttataggagcg 2/DV8*01-3′ SEQ ID NO: 1027 TRAV39*01-5′ gagctgaaagtggaacaaaaccctctgttcctgagcatgcaggagggaaaaaactataccatctactgcaattattcaaccacttcagacagactgtatt SEQ ID NO: 1028 TRAV39*01-3′ cgattaatggcctcacttgataccaaagcccgtctcagcaccctccacatcacagctgccgtgcatgacctctctgccacctacttctgtgccgtggaca SEQ ID NO: 1029 TRAV4*01-5′ cttgctaagaccacccagcccatctccatggactcatatgaaggacaagaagtgaacataacctgtagccacaacaacattgctacaaatgattatatca SEQ ID NO: 1030 TRAV4*01-3′ gcctccctgtttatccctgccgacagaaagtccagcactctgagcctgccccgggtttccctgagcgacactgctgtgtactactgcctcgtgggtgaca SEQ ID NO: 1031 TRAV40*01-5′ agcaattcagtcaagcagacgggccaaataaccgtctcggagggagcatctgtgactatgaactgcacatacacatccacggggtaccctacccttttct SEQ ID NO: 1032 TRAV40*01-3′ aaaacttcggaggcggaaatattaaagacaaaaactcccccattgtgaatattcagtccaggtatcagactcagccgtgtactactgtcttctgggaga SEQ ID NO: 1033 TRAV41*01-5′ aaaaatgaagtggagcagagtcctcagaacctgactgcccaggaaggagaatttatcacaatcaactgcagttactcggtaggaataagtgccttacact SEQ ID NO: 1034 TRAV41*01-3′ aagattaattgccacaataaacatacaggaaaagcacagctccctgcacatcacagcctcccatcccagagactctgcgtctacatctgtgctgtcaga SEQ ID NO: 1035 TRAV5*01-5′ ggagaggatgtggagcagagtcttttcctgagtgtccgagagggagacagctccgttataaactgcacttacacagacagctcctccacctacttatact SEQ ID NO: 1036 TRAV5*01-3′ agactcactgttctattgaataaaaaggataaacatctgtctctgcgcattgcagacacccagactggggactcagctatctacttctgtgcagagagta SEQ ID NO: 1037 TRAV6*01-5′ agccaaaagatagaacagaattccgaggcccgaacattcaggagggtaaaacggccaccctgacctgcaactatacaaactattccccagcatacttac SEQ ID NO: 1038 TRAV6*01-3′ agactgaaggtcacctttgataccacccttaaacagagtttgtttcatatcacagcctcccagcctgcagactcagctacctacctctgtgctctagaca SEQ ID NO: 1039 TRAV6*02-5′ agccaaaagatagaacagaattccgaggccctgaacattcaggagggtaaaacggccaccctgacctgcaactatacaaactattctccagcatacttac SEQ ID NO: 1040 TRAV6*02-3′ gaaagaaagactgaaggtcaccttgataccacccttaaacagagtttgtttcatatcacagcctcccagcctgcagactcagctacctacctctgtgct SEQ ID NO: 1041 TRAV6*03-5′ gaggccctgaacattcaggagggtaaaacggccaccctgacctgcaactatacaaactattctccagcatacttacagtggtaccgacaagatccaggaa SEQ ID NO: 1042 TRAV6*03-3′ gaaagaaagactgaaggtcacctttgataccacccttaaacagagtttgtttcatatcacagcctcccagcctgcagactcagctacctacctctgtgct SEQ ID NO: 1043 TRAV6*04-5′ gaggccctgaacattcaggagggtaaaacggccaccctgacctgcaactatacaaactattctccagcatacttacagtggtaccgacaagatccaggaa SEQ ID NO: 1044 TRAV6*04-3′ gaaagaaagactgaaggtcacctttgataccacccttaaacagagtttgtttcatgtcacagcctcccagcctgcagactcagctacctacctctgtgct SEQ ID NO: 1045 TRAV6*05-5′ gaggccctgaacattcaggagggtaaaacggccaccctgacctgcaactatacgaactattctccagcatacttacagtggtaccgacaagatccaggaa SEQ ID NO: 1046 TRAV6*05-3′ gaaagaaagactgaaggtcacctttgataccacccttaaacagagtttgtttcatatcacagcctcccagcctgcagactcagctacctacctctgtgct SEQ ID NO: 1047 TRAV6*06-5′ agccaaaagatagaacagaattccgaggccctgaacattcaggagggtaaaacggccaccctgacctgcaactatacaaactattctccagcatacttac SEQ ID NO: 1048 TRAV6*06-3′ ccaggaagaggccctgttttcttgctactcatacgtgaaaatgagaaagaaaaaaggaaagaaagactgaaggtcacctttgataccacccttaaccaga SEQ ID NO: 1049 TRAV7*01-5′ gaaaaccaggtggagcacagccctcattttctgggaccccagcagggagacgttgcctccatgagctgcacgtactctgtcagtcgttttaacaatttgc SEQ ID NO: 1050 TRAV7*01-3′ aaaggaagactaaatgctacattactgaagaatggaagcagcttgtacattacagccgtgcagcctgaagattcagccacctatttctgtgctgtagatg SEQ ID NO: 1051 TRAV8-1*01-5′ gcccagtctgtgagccagcataaccaccacgtaattctctctgaagcagcctcactggagttgggatgcaactattcctatggtggaactgttaatctct SEQ ID NO: 1052 TRAV8-1*01-3′ gctttgaggctgaatttataaagagtaaattctcctttaatctgaggaaaccctctgtgcagtggagtgacacagctgagtacttctgtgccgtgaatgc SEQ ID NO: 1053 TRAV8-1*02-5′ gcccagtctgtgagccagcataaccaccacgtaattctctctgaagcagcctcactggagttgggatgcaactattcctatggtggaactgttaatctct SEQ ID NO: 1054 TRAV8-1*02-3′ ttttcaggggatccactggttaaaggcatcaagggcgttgaggctgaatttataaagagtaaattctcctttaatctgaggaaccctctgtgcagtgga SEQ ID NO: 1055 TRAV8-2*01-5′ gcccagtcggtgacccagcttgacagccacgtctctgtctctgaaggaaccccggtgctgctgaggtgcaactactcatcttcttattcaccatctctct SEQ ID NO: 1056 TRAV8-2*01-3′ gttttgaggctgaatttaagaagagtgaaacctccttccacctgacgaaaccctcagcccatatgagcgacgcggctgagtacttctgtgttgtgagtga SEQ ID NO: 1057 TRAV8-2*02-5′ gcccagtcggtgacccagcttagcagccacgtctctgtctctgaaggaaccccggtgctgctgaggtgcaactactcatcttcttattcaccatctctct SEQ ID NO: 1058 TRAV8-2*02-3′ tttaagaagagtgaaacctccttccacctgacgaaaccctcagcccatatgagcgacgcggctgagtacttctgtgttgtgacccgtcacgagctttcag SEQ ID NO: 1059 TRAV8-3*01-5′ gcccagtcagtgacccagcctgacatccacatcactgtctctgaaggagcctcactggagttgagatgtaactattcctatggggcaacaccttatctct SEQ ID NO: 1060 TRAV8-3*01-3′ gctttgaggctgaatttaagaggagtcaatcttccttcaatctgaggaaaccctctgtgcattggagtgatgctgctgagtacttctgtgctgtgggtgc SEQ ID NO: 1061 TRAV8-3*02-5′ gcccagtcagtgacccagcctgacatccacatcactgtctctgaaggagcctcactggagttgagatgtaactattcctatggggcaacaccttatctct SEQ ID NO: 1062 TRAV8-3*02-3′ aggctttgaggctgaatttaagaggagtcaatcttccttcaacctgaggaaaccctctgtgcattggagtgatgctgctgagtacttctgtgctgtggtt SEQ ID NO: 1063 TRAV8-3*03-5′ gcccagtcagtgacccagcctgacatccacatcactgtctctgaaggagcctcactggagttgagatgtaactattcctatggggcaacaccttatctct SEQ ID NO: 1064 TRAV8-3*03-3′ tattaaaggctttgaggctgaatttaagaggagtcaatcttccttcaatctgaggaaaccctctgtgcattggagtgatgcgtcgagtacttctgtgct SEQ ID NO: 1065 TRAV8-4*01-5′ gcccagtcggtgacccagcttggcagccacgtctctgtctctgaaggagccctggttctgctgaggtgcaactactcatcgtctgttccaccatatctct SEQ ID NO: 1066 TRAV8-4*01-3′ gttttgaggctgaatttaagaagagtgaaacctccttccacctgacgaaaccctcagcccatatgagcgacgcggctgagtacttctgtgctgtgagtga SEQ ID NO: 1067 TRAV8-4*02-5′ gcccagtcggtgacccagcttggcagccacgtctctgtctctgaaggagccctggttctgctgaggtgcaactactcatcgtctgttccaccatatctct SEQ ID NO: 1068 TRAV8-4*02-3′ gaatttaagaagagtgaaacctccttccacctgacaaaaccctcagcccatatgagcgacgcggctgagtacttctgtgctgtgagtgatctcgaaccga SEQ ID NO: 1069 TRAV8-4*03-5′ gcccagtcggtgacccagcttggcagccacgtctctgtctctgagggagccctggttctgctgaggtgcaactactcatcgtctgttccaccatatctct SEQ ID NO: 1070 TRAV8-4*03-3′ catcaacggttttgaggctgaatttaagaagagtgaaacctccttccacctgacgaaccctcagcccatatgagcgacgcggctgagtacttctgtgct SEQ ID NO: 1071 TRAV8-4*04-5′ gcccagtcggtgacccagcttggcagccacgtctctgtctctgaacgagccctggttctgctgaggtgcaactactcatcgtctgttccaccatatctct SEQ ID NO: 1072 TRAV8-4*04-3′ aggcatcaacggttttgaggctgaatttaagaagagtgaaacctccttccacctgacgaaaccctcagcccatatgagcgacgcggctgagtacttctgt SEQ ID NO: 1073 TRAV8-4*05-5′ gcccagtcggtgacccagcttggcagccacgtctctgtctctgaaggagccctggttctgctgaggtgcaactactcatcgtctgttccaccatatctct SEQ ID NO: 1074 TRAV8-4*05-3′ ggctgaatttaagaagagtgaaacctccttccacctgacgaaaccctcagcccatatgagcgacgcggctgagtacttctgtgctgtgagtgagtctcca SEQ ID NO: 1075 TRAV8-4*06-5′ ctcttctggtatgtgcaataccccaaccaaggactccagcttctcctgaagtacacatcagcggccaccctggttaaaggcatcaacggttttgaggctg SEQ ID NO: 1076 TRAV8-4*06-3′ gaatttaagaagagtgaaacctccttccacctgacgaaacccgcagcccatatgagcgacgcggctgagtacttctgtgctgtgagtgatctcgaacga SEQ ID NO: 1077 TRAV8-4*07-5′ gttgaaccatatctcttctggtatgtgcaataccccaaccaaggactccagcttctcctgaagtacacaacaggggccaccctggttaaaggcatcaacg SEQ ID NO: 1078 TRAV8-4*07-3′ acggttttgaggctgaatttaaaaagagtgaaacctccttccacctgacgaaaccctcagcccatatgaccgacccggctgagtacttctgtgctgtgag SEQ ID NO: 1079 TRAV8-5*01-5′ gcccagtcagtgacccagcctgacatccgcatcactgtctctgaaggagcctcactggagttgagatgtaactattcctatggggcgatgttgtgggaag SEQ ID NO: 1080 TRAV8-5*01-3′ tggacacttatcacttccccaatcaatacccctgtgatttcctatgcctgtctttactttaatctcttaatcctgtcagctgaggaggatgtatgtcacc SEQ ID NO: 1081 TRAV8-6*01-5′ gcccagtctgtgacccagcttgacagccaagtccctgtctttgaagaagcccctgtggagctgaggtgcaactactcatcgtctgtttcagtgtatctct SEQ ID NO: 1082 TRAV8-6*01-3′ gttttgaggctgaatttaacaagagtcaaacttccttccacttgaggaaaccctcagtccatataagcgacacggctgagtacttctgtgctgtgagtga SEQ ID NO: 1083 TRAV8-6*02-5′ gcccagtctgtgacccagcttgacagccaagtccctgtctttgaagaagcccctgtggagctgaggtgcaactactcatcgtctgtttcagtgtatctct SEQ ID NO: 1084 TRAV8-6*02-3′ gttttgaggctgaatttaacaagagtcaaacttccttccacttgaggaaaccctcagtccatataagcgatacggctgagtacttctgtgctgtgagtga SEQ ID NO: 1085 TRAV8-7*01-5′ acccagtcggtgacccagcttgatggccacatcactgtctctgaagaagcccctctggaactgaagtgcaactattcctatagtggagttccttctctct SEQ ID NO: 1086 TRAV8-7*01-3′ aggctgaatttaagaagagcgaaacctccttctacctgaggaaaccatcaacccatgtgagtgatgctgctgagtacttctgtgctgggtgacaggag SEQ ID NO: 1087 TRAV9-1*01-5′ ggagattcagtggtccagacagaaggccaagtgctcccctctgaaggggattccctgattgtgaactgctcctatgaaaccacacagtacccttcccttt SEQ ID NO: 1088 TRAV9-1*01-3′ gttttgaagccatgtaccgtaaagaaaccacttctttccacttggagaaagactcagttcaagagtcagactccgctgtgtacttctgtgctctgagtga SEQ ID NO: 1089 TRAV9-2*01-5′ ggaaattcagtgacccagatggaagggccagtgactctctcagaagaggccttcctgactataaactgcacgtacacagccacaggatacccttcccttt SEQ ID NO: 1090 TRAV9-2*01-3′ gttttgaagccacataccgtaaagaaaccacttctttccacttggagaaaggctcagttcaagtgcagactcagcggtgtacttctgtgctctgagtga SEQ ID NO: 1091 TRAV9-2*02-5′ ggagattcagtgacccagatggaagggccagtgactctctcagaagaggccttcctgactataaactgcacgtacacagccacaggatacccttcccttt SEQ ID NO: 1092 TRAV9-2*02-3′ caacaaaggttttgaagccacataccgtaaagaaaccacttctttccacttggagaaaggctcagttcaagtgtcagactcagcggtgtacttctgtgct SEQ ID NO: 1093 TRAV9-2*03-5′ ggagattcagtgacccagatggaagggccagtgactctctcagaagaggccttcctgactataaactgcacgtacacagccacaggatacccttcccttt SEQ ID NO: 1094 TRAV9-2*03-3′ caacaaaggttttgaagccacataccgtaaggaaaccacttctttccacttggagaaaggctcagttcaagtgtcagactcagcggtgtacttctgtgct SEQ ID NO: 1095 TRAV9-2*04-5′ ggaaattcagtgacccagatggaagggccagtgactctctcagaagaggccttcctgactataaactgcacgtacacagccacaggatacccttcccttt SEQ ID NO: 1096 TRAV9-2*04-3′ caacaaaggttttgaagccacataccgtaaggaaaccacttctttccacttggagaaaggctcagttcaagtgtcagactcagcggtgtacttctgtgct SEQ ID NO: 1097 TRBV1*01-5′ gatactggaattacccagacaccaaaatacctggtcacagcaatggggagtaaaaggacaatgaaacgtgagcatctgggacatgattctatgtattggt SEQ ID NO: 1098 TRBV1*01-3′ acttcacacctgaatgccctgacagctctcgcttataccttcatgtggtcgcactgcagcaagaagactcagctgcgtatctctgaccagcagccaaga SEQ ID NO: 1099 TRBV10-1*01-5′ gatgctgaaatcacccagagcccaagacacaagatcacagagacaggaaggcaggtgaccttggcgtgtcaccagacttggaaccacaacaatatgttct SEQ ID NO: 1100 TRBV10-1*01-3′ gctacagtgtctctagattaaacacagaggacctccccctcactctggagtctgctgcctcctcccagacatctgtatatttctgcgccagcagtgagtc SEQ ID NO: 1101 TRBV10-1*02-5′ gatgctgaaatcacccagagcccaagacacaagatcacagagacaggaaggcaggtgaccttggcgtgtcaccagacttggaaccacaacaatatgttct SEQ ID NO: 1102 TRBV10-1*02-3′ agatggctacagtgtctctagatcaaacacagaggacctccccctcattctggagtctgctgcctcctcccagactctgtatatttctgcgccagcagt SEQ ID NO: 1103 TRBV10-1*03-5′ aggcaggtgaccttggcgtgtcaccagacttggaaccacaacaatatgttctggtatcgacaagacctgggacatgggctgaggctgatccattactcat SEQ ID NO: 1104 TRBV10-1*03-3′ ctacaaaggagaagtctcagatggctacagtgtctctagatcaaacacagaggacctccccctcactctgtagtctgctgcctcctcccagacatctgt SEQ ID NO: 1105 TRBV10-2*01-5′ gatgctggaatcacccagagcccaagatacaagatcacagagacaggaaggcaggtgaccttgatgtgtcaccagacttggagccacagctatatgttct SEQ ID NO: 1106 TRBV10-2*01-3′ gctatgttgtctccagatccaagacagagaatttccccctcactctggagtcagctacccgctcccagacatctgtgtatttctgcgccagcagtgagtc SEQ ID NO: 1107 TRBV10-2*02-5′ aaggcaggtgaccttgatgtgtcaccagacttggagccacagctatatgttctggtatcgacaagacctgggacatgggctgaggctgatctattactca SEQ ID NO: 1108 TRBV10-2*02-3′ agataaaggagaagtccccgatggctacgttgtctccagatccaagacagagaatttccccctcactctggagtcagctacccgctcccagacatctgtg SEQ ID NO: 1109 TRBV10-3*01-5′ gatgctggaatcacccagagcccaagacacaaggtcacagagacaggaacaccagtgactctgagatgtcaccagactgagaaccaccgctatatgtact SEQ ID NO: 1110 TRBV10-3*01-3′ gctatagtgtctctagatcaaagacagaggatttcctcctcactctggagtccgctaccagctcccagatatctgtgtacttctgtgccatcagtgagtc SEQ ID NO: 1111 TRBV10-3*02-5′ gatgctggaatcacccagagcccaagacacaaggtcacagagacaggaacaccagtgactctgagatgtcatcagactgagaaccaccgctatatgtact SEQ ID NO: 1112 TRBV10-3*02-3′ gctatagtgtctctagatcaaagacagaggatttcctcctcactctggagtccgctaccagctcccagacatctgtgtacttctgtgccatcagtgagtc SEQ ID NO: 1113 TRBV10-3*03-5′ gatgctggaatcacccagagcccaagacacaaggtcacagagacaggaacaccagtgactctgagatgtcaccagactgagaaccaccgctacatgtact SEQ ID NO: 1114 TRBV10-3*03-3′ agaagtctcagatggctatagtgtctctagatcaaagacagaggatttcctcctcactctggagtccgctaccagctcccagacatctgtgtacttctgt SEQ ID NO: 1115 TRBV10-3*04-5′ gatgctggaatcacccagagcccaagacacaaggtcacagagacaggaacaccagtgactctgagatgtcaccagactgagaaccaccgctacatgtact SEQ ID NO: 1116 TRBV10-3*04-3′ agaagtctcagatggctatagtgtctctagatcaaagacagaggatttcctcctcactctggagtccgctaccagctcccagacatctgtgtacttctgt SEQ ID NO: 1117 TRBV11-1*01-5′ gaagctgaagttgcccagtcccccagatataagattacagagaaaagccaggctgtggctttttggtgtgatcctatttctggccatgctaccctttact SEQ ID NO: 1118 TRBV11-1*01-3′ gattttctgcagagaggctcaaaggagtagactccactctcaagatccagcctgcagagcttggggactcggccatgtatctctgtgccagcagcttagc SEQ ID NO: 1119 TRBV11-2*01-5′ gaagctggagttgcccagtctcccagatataagattatagagaaaaggcagagtgtggctttttggtgcaatcctatatctggccatgctaccctttact SEQ ID NO: 1120 TRBV11-2*01-3′ gattttctgcagagaggctcaaaggagtagactccactctcaagatccagcctgcaaagcttgaggactcggccgtgtatctctgtgccagcagcttaga SEQ ID NO: 1121 TRBV11-2*02-5′ gaagctggagttgcccagtctcccagatataagattatagagaaaaggcagagtgtggctttttggtgcaatcctatatctggccatgctaccctttact SEQ ID NO: 1122 TRBV11-2*02-3′ ggatcgattttctgcagagaggctcaaaggagtagactccactctcaagatccagcctgcaaagcttgagaactcggccgtgtatctctgtgccagcagt SEQ ID NO: 1123 TRBV11-2*03-5′ gaagctggagttgcccagtctcccagatataagattatagagaaaaggcagagtgtggctttttggtgcaatcctatatctggccatgctaccctttact SEQ ID NO: 1124 TRBV11-2*03-3′ ggatcgattttctgcagagaggctcaaaggagtagactccactctcaagatccaacctgcaaagcttgaggactcggcgtgtatctctgtgcagcagc SEQ ID NO: 1125 TRBV11-3*01-5′ gaagctggagtggttcagtctcccagatataagattatagagaaaaaacagcctgtggctttttggtgcaatcctatttctggccacaataccctttact SEQ ID NO: 1126 TRBV11-3*01-3′ gattttctgcagagaggctcaaaggagtagactccactctcaagatccagcctgcagagcttggggactcggccgtgtatctctgtgccagcagcttaga SEQ ID NO: 1127 TRBV11-3*02-5′ gaagctggagtggttcagtctcccagatataagattatagagaaaaagcagcctgtggctttttggtgcaatcctatttctggccacaataccctttact SEQ ID NO: 1128 TRBV11-3*02-3′ ggatcgattttctgcagagaggctcaaaggagtagactccactctcaagatccagcctgcagagcttggggactcggccgtgtatctctgtgccagcagc SEQ ID NO: 1129 TRBV11-3*03-5′ ggtctcccagatataagattatagagaagaaacagcctgtggctttttggtgcaatccaatttctggccacaataccctttactggtacctgcagaactt SEQ ID NO: 1130 TRBV11-3*03-3′ ggatcgattttctgcagagaggctcaaaggagtagactccactctcaagatccagccagcagagcttggggactcggccatgtatctctgtgccagcagc SEQ ID NO: 1131 TRBV12-1*01-5′ gatgctggtgttatccagtcacccaggcacaaagtgacagagatgggacaatcagtaactctgagatgcgaaccaatttcaggccacaatgatcttctct SEQ ID NO: 1132 TRBV12-1*01-3′ gattctcagcacagatgcctgatgtatcattctccactctgaggatccagcccatggaacccagggacttgggcctatatttctgtgccagcagctttgc SEQ ID NO: 1133 TRBV12-2*01-5′ gatgctggcattatccagtcacccaagcatgaggtgacagaaatgggacaaacagtgactctgagatgtgagccaatttttggccacaatttccttttct SEQ ID NO: 1134 TRBV12-2*01-3′ gattctcagctgagaggcctgatggatcattctctactctgaagatccagcctgcagagcagggggactcggccgtgtatgtctgtgcaagtcgcttagc SEQ ID NO: 1135 TRBV12-3*01-5′ gatgctggagttatccagtcaccccgccatgaggtgacagagatgggacaagaagtgactctgagatgtaaaccaatttcaggccacaactcccttttct SEQ ID NO: 1136 TRBV12-3*01-3′ gattctcagctaagatgcctaatgcatcattctccactctgaagatccagccctcagaacccagggactcagctgtgacttctgtgccagcagtttagc SEQ ID NO: 1137 TRBV12-4*01-5′ gatgctggagttatccagtcaccccggcacgaggtgacagagatgggacaagaagtgactctgagatgtaaaccaatttcaggacacgactaccttttct SEQ ID NO: 1138 TRBV12-4*01-3′ gattctcagctaagatgcctaatgcatcattctccactctgaagatccagccctcagaacccagggactcagctgtgacttctgtgccagcagtttagc SEQ ID NO: 1139 TRBV12-4*02-5′ gatgctggagttatccagtcacccggcacgaggtgacagagatgggacaagaagtgactctgagatgtaaaccaatttcaggacatgactaccttttct SEQ ID NO: 1140 TRBV12-4*02-3′ tcgattctcagctaagatgcctaatgcatcattctccactctgaggatcagccctcagaacccagggactcagctgtgtacttctgtgccagcagttta SEQ ID NO: 1141 TRBV12-5*01-5′ gatgctagagtcacccagacaccaaggcacaaggtgacagagatgggacaagaagtaacaatgagatgtcagccaattttaggccacaatactgttttct SEQ ID NO: 1142 TRBV12-5*01-3′ gattctcagcagagagcctgatgcaactttagccactctgaagatccagccctcagaacccagggactcagctgtgtatttttgtgctagtggtttggt SEQ ID NO: 1143 TRBV13*01-5′ gctgctggagtcatccagtccccaagacatctgatcaaagaaaagagggaaacagccactctgaaatgctatcctatccctagacacgacactgtctact SEQ ID NO: 1144 TRBV13*01-3′ gattctcagctcaacagttcagtgactatcattctgaactgaacatgagctccttggagctgggggactcagccctgtacttctgtgccagcagcttagg SEQ ID NO: 1145 TRBV13*02-5′ gctgctggagtcatccagtccccaagacatttgatcagagaaaagagggaaacagccactctgaaatgctatcctatccctagacacgacactgtctact SEQ ID NO: 1146 TRBV13*02-3′ tgatcgattctcagctcaacagttcagtgactatcattctgaactgaacatgagctccttggagctgggggactcagcctgtacttctgtgccagcagc SEQ ID NO: 1147 TRBV14*01-5′ gaagctggagttactcagttccccagccacagcgtaatagagaagggccagactgtgactctgagatgtgacccaatttctggacatgataatctttatt SEQ ID NO: 1148 TRBV14*01-3′ gattcttagctgaaaggactggagggacgtattctactctgaaggtgcagcctgcagaactggaggattctggagtttatttctgtgccagcagccaaga SEQ ID NO: 1149 TRBV14*02-5′ gaagctggagttactcagttccccagccacagcgtaatagagaagggccagactgtgactctgagatgtgacccaatttctggacatgataatctttatt SEQ ID NO: 1150 TRBV14*02-3′ caatcgattcttagctgaaaggactggagggacgtattctactctgaaggtgcagcctgcagaactggaggattctggagtttatttctgtgccagcagc SEQ ID NO: 1151 TRBV15*01-5′ gatgccatggtcatcagaacccaagataccaggttacccagtttggaaagccagtgaccctgagttgttctcagactttgaaccataacgtcatgtact SEQ ID NO: 1152 TRBV15*01-3′ acttccaatccaggaggccgaacacttctttctgctttcttgatatccgctcaccaggcctgggggacacagccatgtacctgtgtgccaccagcagaga SEQ ID NO: 1153 TRBV15*02-5′ gatgccatggtcatccagaacccaagataccaggttacccagtttggaaagccagtgaccctgagttgttctcagactttgaaccataacgtcatgtact SEQ ID NO: 1154 TRBV15*02-3′ ggtgaagaagtcgcccagactccaaaacatcttgtcagaggggaaggacagaaagcaaaattatattgtgccccaataaaaggacaagttatgtttttt SEQ ID NO: 1155 TRBV15*03-5′ gatgccatggtcatccagaacccaagataccgggttacccagtttggaaagccagtgaccctgagttgttctcagactttgaaccataacgtcatgtact SEQ ID NO: 1156 TRBV15*03-3′ tgataacttccaatccaggaggccgaacacttctttctgctttctagacatccgctcaccaggcctgggggacgcagccatgtaccagtgtgccaccagc SEQ ID NO: 1157 TRBV16*01-5′ ggtgaagaagtcgcccagactccaaaacatcttgtcagaggggaaggacagaaagcaaaattatattgtgccccaataaaaggacacagttatgtttttt SEQ ID NO: 1158 TRBV16*01-3′ gattttcagctaagtgcctcccaaattcaccctgtagccttgagatccaggctacgaagcttgaggattcagcagtgtatttttgtgccagcagccaatc SEQ ID NO: 1159 TRBV16*02-5′ ggtgaagaagtcgcccagactccaaaacatcttgtcagaggggaaggacagaaagcaaaattatattgtgccccaataaaaggacacagttaggtttttt SEQ ID NO: 1160 TRBV16*02-3′ gattttcagctaagtgcctcccaaattcaccctgtagccttgagatccaggctacgaagcttgaggattcagcagtgtatttttggccagcagccaatc SEQ ID NO: 1161 TRBV16*03-5′ ggtgaagaagtcgcccagactccaaaacatcttgtcagaggggaaggacagaaagcaaaattatattgtgccccaataaaaggacacagttatgtttttt SEQ ID NO: 1162 TRBV16*03-3′ ggaaagattttcagctaagtgcctcccaaattcaccctgtagccttgagatccaggctacgaagcttgaggattcagcagtgtatttttgtgccagcagc SEQ ID NO: 1163 TRBV17*01-5′ gagcctggagtcagccagacccccagacacaaggtcaccaacatgggacaggaggtgattctgaggtgcgatccatcttctggtcacatgtttgttcact SEQ ID NO: 1164 TRBV17*01-3′ aacgattcacagctgaaagacctaacggaacgtcttccacgctgaagatccatcccgcagagccgagggactcagccgtgtatctctacagtagcggtgg SEQ ID NO: 1165 TRBV18*01-5′ aatgccggcgtcatgcagaacccaagacacctggtcaggaggaggggacaggaggcaagactgagatgcagcccaatgaaaggacacagtcatgtttact SEQ ID NO: 1166 TRBV18*01-3′ gattttctgctgaatttcccaaagagggccccagcatcctgaggatccagcaggtagtgcgaggagattcggcagcttatttctgtgccagctcaccacc SEQ ID NO: 1167 TRBV19*01-5′ gatggtggaatcactcagtccccaaagtacctgttcagaaaggaaggacagaatgtgaccctgagttgtgaacagaatttgaaccacgatgccatgtact SEQ ID NO: 1168 TRBV19*01-3′ ggtacagcgtctctcgggagaagaaggaatcctttcctctcactgtgacatcggcccaaagaacccgacagctttctatctctgtgccagtagtataga SEQ ID NO: 1169 TRBV19*02-5′ gatggtggaatcactcagtccccaaagtacctgttcagaaaggaaggaacagaatgtgaccctgagttgtgaacagaatttgaaccacgatgccatgtact SEQ ID NO: 1170 TRBV19*02-3′ ggtacagcgtctctcgggagaagaaggaatcctttcctctcactgtgacatcggcccaaaagaacccgacagctttctatctctgtgccagtagtataga SEQ ID NO: 1171 TRBV19*03-5′ gatggtggaatcactcagtccccaaagtacctgttcagaaaggaaggacagaatgtgaccctgagttgtgaacagaatttgaaccatgatgccatgtact SEQ ID NO: 1172 TRBV19*03-5′ tgaagggtacagcgtctctcgggagaagaaggaatcctttcctctcactgtgacatcggcccaaaagaacccgacagctttctatctctgtgccagtagc SEQ ID NO: 1173 TRBV2*01-5′ gaacctgaagtcacccagactcccagccatcaggtcacacagatgggacaggaagtgatcttgcgctgtgtccccatctctaatcacttatacttctatt SEQ ID NO: 1174 TRBV2*01-3′ aattctcagttgaaaggcctgatggatcaaatttcactctgaagatccggtccacaaagctggaggactcagccatgtacttctgtgccagcagtgaagc SEQ ID NO: 1175 TRBV2*02-5′ gaacctgaagtcacccagactcccagccatcaggtcacacagatgggacaggaagtgatcttgcactgtgtccccatctctaatcacttatacttctatt SEQ ID NO: 1176 TRBV2*02-3′ tgatcaattctcagttgaaaggcctgatggatcaaatttcactctgaagatccggtccacaaagctggaggactcagccatgtacttctgtgccagcagt SEQ ID NO: 1177 TRBV2*03-5′ gaacctgaagtcatccagactcccagccatcaggtcacacagatgggacaggaagtgatcttgcgctgtgtccccatctctaatcacttatacttctatt SEQ ID NO: 1178 TRBV2*03-3′ tcaattctcagttgagaggcctgatggatcaaatttcactctgaagatccggtccacaaagctggaggactcagccatgtacttctgtgccagcagtgaa SEQ ID NO: 1179 TRBV20-1*01-5′ ggtgctgtcgtctctcaacatccgagctgggttatctgtaagagtggaacctctgtgaagatcgagtgccgttccctggactttcaggccacaactatgt SEQ ID NO: 1180 TRBV20-1*01-3′ acaagtttctcatcaaccatgcaagcctgaccttgtccactctgacagtgaccagtgcccatcctgaagacagcagcttctacatctgcagtgctagaga SEQ ID NO: 1181 TRBV20-1*02-5′ ggtgctgtcgtctctcaacatccgagcagggttatctgtaagagtggaacctctgtgaagatcgagtgccgttccctggactttcaggccacaactatgt SEQ ID NO: 1182 TRBV20-1*02-3′ gaaggacaagtttctcatcaaccatgcaagcctgaccttgtccactctgacagtgaccagtgcccatcctgaagacagcagcttctacatctgcagtgct SEQ ID NO: 1183 TRBV20-1*03-5′ ggtgctgtcgtctctcaacatccgagctgggttatctgtaagagtggaacctctgtgaagatcgagtgccgttccctggactttcaggccacaactatgt SEQ ID NO: 1184 TRBV20-1*03-3′ gaaggacaagtttctcatcaaccatgcaagcctgaccttgtccactctgacagtgaccagtgcccatcctgaagacagcagcttctacatctgcagtgct SEQ ID NO: 1185 TRBV20-1*04-5′ ggtgctgtcgtctctaacatccgagcagggttatctgtaagagtggaacctctgtgaagatcgagtgccgttccttggactttcaggccacaactatgt SEQ ID NO: 1186 TRBV20-1*04-3′ ggacaagtttctcatcaaccatgcaagcctgaccttgtccactctgacagtgaccagtgcccatcctgaagacagcagcttctacatctgcagtgctagt SEQ ID NO: 1187 TRBV20-1*05-5′ ggtgccgtcgtctctcaacatccgagcagggttatctgtaagagtggaacctctgtgaagatcgagtgccgttccctggactttcaggccacaactatgt SEQ ID NO: 1188 TRBV20-1*05-3′ ggacaagtttctcatcaaccatgcaagcctgaccttgtccactctgacagtgaccgtgcccatcctgaagacagcagcttctacatctgcagtgctaga SEQ ID NO: 1189 TRBV20-1*06-5′ ggtgctgtcgtctctcaacatccgagtagggttatctgtaagagtggaacctctgtgaagatcgagtgccgttccctggactttcaggccacaactatgt SEQ ID NO: 1190 TRBV20-1*06-3′ gaaggacaagtttctcatcaaccatgcaagcctgaccttgtccactctgacagtgaccagtgcccatcctgaagacagcagcttctacatctgcagtgct SEQ ID NO: 1191 TRBV20-1*07-5′ ggtgctgtcgtctctcaacatccgagcagggttatctgtaagagtggaacctctgtgaagatcgagtgccgttccctggactttcaggccacaactatgt SEQ ID NO: 1192 TRBV20-1*07-3′ ggacaagtttctcatcaaccatgcaagcctgaccttgtccactctgacagtgaccagtgcccatcctgaagacagcagcttctacatctgcagtgctaga SEQ ID NO: 1193 TRBV20/OR9- agtgctgtcgtctctcaacatccgagcagggttatctgtaagagtggaacctctgtgaacatcgagtgccgttccctggactttcaggccacaactatgt 2*01-5′ SEQ ID NO: 1194 TRBV20/OR9- acaagtttcccatcaaccatccaaacctgaccttctccgctctgacagtgaccagtgcccatcctgaagacagcagcttctacatctgcagtgctagaga 2*01-3′ SEQ ID NO: 1195 TRBV20/OR9- ggtgctgtcgtctctcaacatccgagcagggttatctgtaagagtggaacctctgtgaacatcgagtgccgttccctggactttcaggccacaactatgt 2*02-5′ SEQ ID NO: 1196 TRBV20/OR9- gaaggacaagtttcccatcaaccatccaaacctgaccttctccgctctgacagtgacctgtgcccatcctgaagacagcagcttctacatctgcagtgct 2*02-3′ SEQ ID NO: 1197 TRBV20/OR9- agtgctgtcgtctctcaacatccgagcagggttatctgtaagagtggaacctctgtgaacatcgagtgccgttccctggactttcaggccacaactatgt 2*02-5′ SEQ ID NO: 1198 TRBV20/OR9- acaagtttcccatcaactatccaaacctgaccttctccgctctgacagtgaccagtgcccatcctgaagacagcagcttctacatctgcagtgctagaga 2*03-3′ SEQ ID NO: 1199 TRBV21-1*01-5′ gacaccaaggtcacccagagacctagacttctggtcaaagcaagtgaacagaaagcaaagatggattgtgttcctataaaagcacatagttatgtttact SEQ ID NO: 1200 TRBV21-1*01-3′ gatttttagcccaatgctccaaaaactcatcctgtaccttggagatccagtccacggagtcaggggacacagcactgtatttctgtgccagcagcaaagc SEQ ID NO: 1201 TRBV21/OR9- gacaccaaggtcacccagagacctagatttctggtcaaagcaaatgaacagaagcaaagatggactgtgttcctataaaaagacatagttatgtttact 2*01-5′ SEQ ID NO: 1202 TRBV21/OR9- gattttcagcccaatgcccccaaaactcaccctgtaccttggagatccagtccacggagtcaggagacacagcacggtatttctgtgccaacagcaagc 2*01-3′ SEQ ID NO: 1203 TRBV22-1*01-5′ gatgctgacatctatcagatgccattccagctcactggggctggatgggatgtgactctggagtggaaacggaatttgagacacaatgacatgtactgct SEQ ID NO: 1204 TRBV22-1*01-3′ aggctacgtgtctgccaagaggagaaggggctatttcttctcagggtgaagttggcccacaccagccaaacagctttgtacttctgtcctgggagcgcac SEQ ID NO: 1205 TRBV22/OR9- gatgctgacatctatcagacgccattccagctcactggggctggatgggatgtgaccctggagtagaaacaatttgagacacaatgacatgtactggtac 2*01-5′ SEQ ID NO: 1206 TRBV22/OR9- ggctacggtgtctcccgagaggagaaggggctgtttcttctcatggtgaagctggcccacaccagccaaacagctctgtacttctgtcctgggagtgcac 2*01-3′ SEQ ID NO: 1207 TRBV23-1*01-5′ catgccaaagtcacacagactccaggacatttggtcaaaggaaaaggacagaaaacaaagatggattgtacccccgaaaaaggacatacttttgtttatt SEQ ID NO: 1208 TRBV23-1*01-3′ gattctcatctcaatgccccaagaacgcaccctgcagcctggcaatcctgtcctcagaaccgggagacacggcactgtatctctgcgccagcagtcaatc SEQ ID NO: 1209 TRBV23/OR9- catgccaaagtcacacagactccaggatatttggtcaaaggaaaaggaaggaaaacaaagatgtattgtacccccaaaacggacatacttttgtttgtt 2*01-5′ SEQ ID NO: 1210 TRBV23/OR9- gatgcacaagaagcgattctcatctcaatgccccaagaacccaccctgcagcctggcaatcctgtcctcggaacgggagacaccgcactgtatctctgt 2*01-3′ SEQ ID NO: 1211 TRBV23/OR9- catgccaaagtcacacagactccaggatatttggtcaaaggaaaaggaaggaaaacaaagatgtattgtacccccaaaaacggacatacttttgtttgttt 2*02-5′ SEQ ID NO: 1212 TRBV23/OR9- gtttttgatttcctttcagaatgaacaagttcttcaagaaatggagatgcacaagaagcgattctcatctcaatgccccaagaacgcaccctgcagcctg 2*02-3′ SEQ ID NO: 1213 TRBV24-1*01-5′ gatgctgatgttacccagaccccaaggaataggatcacaaagacaggaaagaggattatgctggaatgttctcagactaagggtcatgatagaatgtact SEQ ID NO: 1214 TRBV24-1*01-3′ ataccagtgtctctcgacaggcacaggctaaattctccctgtccctagagtctgccatccccaaccagacagctctttacttctgtgccaccagtgatttg SEQ ID NO: 1215 TRBV24/OR9- gatgctgatgttacccagaccccaaggaataggatcacaaagacaggaaagaggattatgctggaatgttctcagactaagggtcatgatagaatgtact 2*01-5′ SEQ ID NO: 1216 TRBV24/OR9- atacagtgtctctcgacaggcacaggctaaattctccctgtccctagagtctgccacccccaaccgacagctctttacttctgtgccaccagtgatttg 2*01-3′ SEQ ID NO: 1217 TRBV24/OR9- gatgctgatgttatccagaccccaaggaataggatcacaaagacaggaaagaggattatgctggcatgttctcagactaagggtcatgatggaatgtact 2*02-5′ SEQ ID NO: 1218 TRBV24/OR9- cagttgatctattgctcctttgatgtcaaaatatataaacaaaagagagatctctgatggatacagtgtctcttgacaggaacaggctaaattctccctg 2*02-3′ SEQ ID NO: 1219 TRBV24/OR9- gatgctgatgttatccagaccccaaggaataggatcacaaagacaggaaagaggattatgctggaatgttctcagactaagggtcatgatggaatgtact 2*03-5′ SEQ ID NO: 1220 TRBV24/OR9- agtgtctcttgacaggaacaggctaaattctccctgtccctagagcctgccacccccaaccagacagcttctaggttacttcagtgccaccagtgatttc 2*03-3′ SEQ ID NO: 1221 TRBV25-1*01-5′ gaagctgacatctaccagaccccaagataccttgttatagggacaggaaagaagatcactctggaatgttctcaaaccatgggccatgacaaaatgtact SEQ ID NO: 1222 TRBV25-1*01-3′ agtcaatagtctccagaataaggacggagcattttcccctgaccctggagtctgccaggccctcacatacctctcagtacctctgtgccagcagtgaata SEQ ID NO: 1223 TRBV25/OR9- gaagctgaaatctaccagaccccaagacaccgtgttataggggcaggaaagaagatcactctggaatgttctcaaaccatgggccatgacaaaatgtat 2*01-5′ SEQ ID NO: 1224 TRB25/OR9- agtcaacagtctccagaataaggatagagcgttttcccctgaccctggagtctgccagcccctcacatacctctcagtacctctgtgccagcagtgaata 1*01-3′ SEQ ID NO: 1225 TRBV25/OR9- gaagctgaaatctaccagaccccaagacaccgtgttataggggcaggaaagaagatcactctggaatgttctcaaaccatgggccatgacaaaatgtact 2*02-5′ SEQ ID NO: 1226 TRBV25/OR9- gagttaattccacagagaagggagatctttgctctgagtcaacagtctccagaataaggatagagcgttttcccctgaccctggagtctgccagcccctc 2*02-3′ SEQ ID NO: 1227 TRBV26*01-5′ gatgctgtagttacacaattcccaagacacagaatcattgggacaggaaaggaattcattctacagtgttccccagaatatgaatcatgttacaatgtact SEQ ID NO: 1228 TRBV26*01-3′ ggtatcatgtttcttgaaatactatagcatcttttcccctgaccctgaagtctgccagcaccaaccagacatctgtgtatctctatgccagcagttcatc SEQ ID NO: 1229 TRBV26/OR9- gatgctgtagttacacaattctcaagacacagaatcattgggacaggaaaggaattcattctactgtgtccccagaatatgaatcatgttgcaatgtact 2*01-5′ SEQ ID NO: 1230 TRBV26/OR9- ggtatcatgtttcttgaaatactatagcatcttttctcctgaccctgaagtcgctagcaccaaccagacatgtgtgtatctctgcgcagcagttcatc 2*01-3′ SEQ ID NO: 1231 TRBV26/OR9- gatgctgtagttacacaattcccaagacacagaatcattgggacaggaaaggaattcattctactgtgccccagaatatgaatcatgttgcaatgtact 2*02-5′ SEQ ID NO: 1232 TRBV26/OR9- ggtatcatgtttcttgaaatactatagcatcttttctcctgaccctgaagtctgctagcaccaaccagacatgtgtgtatctctgcgccagcagttcatc 2*02-3′ SEQ ID NO: 1233 TRBV27*01-5′ gaagcccaagtgacccagaacccaagatacctcatcacagtgactggaaagaagttaacagtgacttgttctcagaatatgaaccatgagtatatgtcct SEQ ID NO: 1234 TRBV27*01-3′ ggtacaaagtctctcgaaaagagaagaggaatttccccctgatcctggagtcgcccagccccaaccagacctctctgtacttctgtgccagcagtttatc SEQ ID NO: 1235 TRBV28*01-5′ gatgtgaaagtaacccagagctcgagatatctagtcaaaaggacgggagagaaagtttttctggaatgtgtccaggatatggaccatgaaaatatgttct SEQ ID NO: 1236 TRBV28*01-3′ ggtacagtgtctctagagagaagaaggagcgcttctccctgattctggagtccgccagcaccaaccagacatctatgtacctctgtgccagcagtttatg SEQ ID NO: 1237 TRBV29-1*01-5′ agtgctgtcatctctcaaaagccaagcagggatatctgtcaacgtggaacctccctgacgatccagtgtcaagtcgatagccaagtcaccatgatgttct SEQ ID NO: 1238 TRBV29-1*01-3′ acaagtttcccatcagccgcccaaacctaacatttcaactctgactgtgagcaacatgagccctgaagacagcagcatatatctctgcagcgttgaaga SEQ ID NO: 1239 TRBV29-1*02-5′ agtgctgtcatctctcaaaagccaagcagggatatctgtcaacgtggaacctccctgacgatccagtgtcaagtcgatagccaagtcaccatgatgttc SEQ ID NO: 1240 TRBV29-1*02-3′ tgacaagtttcccatcagccgccaaacctaacattctcaagtctgactgtgagcaacatgagccctgaagacagcagcatatatctctgcagcgttgaa SEQ ID NO: 1241 TRBV29-1*03-5′ acgatccagtgtcaagtcgatagccaagtcaccatgatattctggtaccgtcagcaacctggacagagcctgacactgatcgcaactgcaaatcagggct SEQ ID NO: 1242 TRBV29-1*03-3′ tgacaagtttcccatcagccgcccaaacctaacattctcaactctgactgtgagcaacatgagccctgaagacagcagcatatatctctgcagcgcgggc SEQ ID NO: 1243 TRBV29/OR9- agtgctgtcatctctcaaaagccaagcagggatatctgtcaacgtggaacctccatgatgatccagtgtcaagtcgacagccaagtcaccatgatgttct 2*01-5′ SEQ ID NO: 1244 TRBV29/OR9- acaagtttcccatcagccgcccaaacctaacattctcaactctgactgtgagcaacaggagacctgaagacagcagcatatacctctgcagcgttgaaga 2*01-3′ SEQ ID NO: 1245 TRBV29/OR9- agtgctgtcatctctcaaaagccaagcagggatatctgtcaacgtggaacctccatgatgatccagtgtcaagtcgacagccaagtcaccatgatgttct 2*02-5′ SEQ ID NO: 1246 TRBV29/OR9- acaagtttcccatcagccgcccaaacctaacattctcaactctgactgtgagcaacaggagacctgaagacagcagcatatacctctgcagcgttgaaga 2*02-3′ SEQ ID NO: 1247 TRBV3-1*01-5′ gacacagctgtttcccagactccaaaatacctggtcacacagatgggaaacgacaagtccattaaatgtgaacaaaatctgggccatgatactatgtatt SEQ ID NO: 1248 TRBV3-1*01-3′ gcttctcacctaaatctccagacaaagctcacttaaatcttcacatcaattccctggagcttggtgactctgctgtgtatttctgtgccagcagccaaga SEQ ID NO: 1249 TRBV3-1*02-5′ gacacagctgtttcccagactccaaaatacctggtcacacagatgggaaacgacaagtccattaaatgtgaacaaaatctgggccatgatactatgtatt SEQ ID NO: 1250 TRBV3-1*02-3′ tccaaatcgattctcacctaaatctccagacaaagctaaattaaatcttcacatcaattccctggagcttggtgactctgctgtgtatttctgtgccagc SEQ ID NO: 1251 TRBV3-2*01-5′ gacacagccgtttcccagactccaaaatacctggtcacacagatgggaaaaaaggagtctcttaaatgagaacaaaatctgggccataatgctatgtatt SEQ ID NO: 1252 TRBV3-2*01-3′ gcttctcacctgactctccagacaaagctcatttaaatcttcacatcaattccctggagcttggtgactctgctgtgtatttctgtgccagcagccaaga SEQ ID NO: 1253 TRBV3-2*02-5′ gacacagccgtttcccagactccaaaaatacctggtcacacagatgggaaaaaaggagtctcttaaatgagaacaaaatctgggccataatgctatgtatt SEQ ID NO: 1254 TRBV3-2*02-3′ gcttctcacctgactctccagacaaagttcatttaaatcttcacatcaattccctggagctrtggtgactctgctgtgtatttctgtccagagccaaga SEQ ID NO: 1255 TRBV3-2*03-5′ gacacagccgtttcccagactccaaaatacctggtcacacagacgggaaaaaaggagtctcttaaatgagacaaaatctgggccataatgctatgtatt SEQ ID NO: 1256 TRBV3-2*03-3′ tcgcttctcacctgactctccagacaaagttcatttaaatcttcacatcaattccctggagcttggtgactctgctgtgtatttctgtgccagcagccaa SEQ ID NO: 1257 TRBV30*01-5′ tctcagactattcatcaatggccagcgaccctggtgcagcctgtgggcagcccgctctctctggagtgcactgtggagggaacatcaaaccccaacctat SEQ ID NO: 1258 TRBV30*01-3′ agaatctctcagcctccagaccccaggaccggcagttcatcctgagttctaagaagctccttctcagtgactctggcttctatctctgtgcctggagtgt SEQ ID NO: 1259 TRBV30*02-5′ tctcagactattatcaatggccagcgaccctggtgcagcctgtgggcagcccgctctctctggagtgcactgtggagggaacatcaaaccccaacctat SEQ ID NO: 1260 TRBV30*02-3′ agaatctctcagcctccagaccccaggaccggcagttcatcctgagttctaagaagctcctcctcagtgactctggcttctatctctgtgcctggagtgt SEQ ID NO: 1261 TRBV30*04-5′ actattcatcaatggccagcgaccctggtgcagcctgtgggcagcccgctctctctggagtgcactgtggagggaacatcaaaccccaacctatactggt SEQ ID NO: 1262 TRBV30*04-3′ ccagaatctctcagcctccagaccccaggaccggcagttcattctgagttctaagaagctcctcctcagtgactctggcttctatctctgtgcctggagt SEQ ID NO: 1263 TRBV30*05-5′ tctcagactattcatcaatggccagcgaccctggtgcagcctgtgggcagcccgctctccctggagtgcactgtggagggaacatcaaaccccaacctat SEQ ID NO: 1264 TRBV30*05-3′ ccagaatctctcagcctccagaccccaggaccggcagttcatcctgagttctaagaagctccttctcagtgactctggcttctatctctgtgcctgggga SEQ ID NO: 1265 TRBV4-1*01-5′ gacactgagttacccagacaccaaaacacctggtcatgggaatgacaaataagaagtctttgaaatgtgaacaacatatggggcacagggctatgtatt SEQ ID NO: 1266 TRBV4-1*01-3′ gcttctacctgaatgccccaacagctctctcttaaaccttcacctacacgccctgcagccagaagactcagccctgtatctctgcgccagcagccaaga SEQ ID NO: 1267 TRBV4-1*02-5′ cacctggtcatgggaatgacaaataagaagtctttgaaatgtgaacaacatatggggcacagggcaatgtattggtacaagcagaaagctaagaagccac SEQ ID NO: 1268 TRBV4-1*02-3′ tcgcttctcacctgaatgccccaacagctctctcttaaaccttcacctacacgccctgcagccagaagactcagccctgtatctctgcgccagcagccaa SEQ ID NO: 1269 TRBV4-2*01-5′ gaaacgggagttacgcagacaccaagacacctggtcatgggaatgacaaataagaagtctttgaaatgtgaacaacatctggggcataacgctatgtatt SEQ ID NO: 1270 TRBV4-2*01-3′ gcttctcacctgaatgccccaacagctctcacttattccttcacctacacaccctgcagccagaagactcggccctgtatctctgtgccatgcagccaaga SEQ ID NO: 1271 TRBV4-2*02-5′ gaaacgggagttacgcagacaccaagacacctggtcatgggaatgacaaataagaagtctttgaaatgtgaacaacatctggggcataacgctaatgtatt SEQ ID NO: 1272 TRBV4-2*02-3′ aagtcgcttctcacctgaatgccccaacagctctcacttatgccttcacctacacaccctgcagccagaagactcggccctgtatctctgtgccagcacc SEQ ID NO: 1273 TRBV4-3*01-5′ gaaacgggagttacgcagacaccaagacacctggtcatgggaatgacaaataagaagtctttgaaatgtgaacaacatctgggtcataacgctaatgtatt SEQ ID NO: 1274 TRBV4-3*01-3′ gcttctcatctgaatgccccaacagctctcacttattccttcacctacacaccctgcagccagaagactcggccctgtatctctgcgccagcagccaaga SEQ ID NO: 1275 TRBV4-3*02-5′ gaaacgggagttacgcagacaccaagacacctggtcatgggaatgacaaataagaagtctttgaaatgtgaacaacatctgggtcataacgctatgtatt SEQ ID NO: 1276 TRBV4-3*02-3′ aagtcgcttctcacctgaatgccccaacagctctcacttatcccttcacctacacaccctgcagccagaagactcggccctgtatctctgcgccagcagc SEQ ID NO: 1277 TRBV4-3*03-5′ gaaacgggagttacgcagacaccaagacacctggtcatgggatgacaaataagaagtctttgaaagtgaacaacatctgggtcataacgctatgtatt SEQ ID NO: 1278 TRBV4-3*03-3′ aagtcgcttctcactgaatgccccaacagctctcacttattccttcacctacacaccctgcagccagaagactcggccctgtatctctgcgccagcagc SEQ ID NO: 1279 TRBV4-3*04-5′ aagaagtctttgaaatgtgaacaacatctggggcataacgctatgtattggtacaagcaaagtgctaagaagccazctggagctcatgtttgtctacagtc SEQ ID NO: 1280 TRBV4-3*04-3′ aagtcgcttctcacctgaatgccccaacagctctcacttattccttcacctacacaccctgcagccagaagactcggccctgtatctctgcgccagcagc SEQ ID NO: 1281 TRBV5-1*01-5′ aaggctggagtcactcaaactccaagatatctgatcaaaacgagaggacagcaagtgacactgagctgctcccctatctctgggcataggagtgtatcct SEQ ID NO: 1282 TRBV5-1*01-3′ cgattctcagggcgccagttctctaactctcgctctgagatgaatgtgagcaccttggagctgggggactcggccctttatctttgcgccagcagcttgg SEQ ID NO: 1283 TRBV5-1*02-5′ agggctggggtcactcaaactccaagacatctgatcaaaacgagaggacagcaagtgacactgggctgctcccctatctctgggctaggagtgtatcct SEQ ID NO: 1284 TRBV5-1*02-3′ tcgattctcagggcgccagttctctaactctcgctctgagatgaatgtgagcaccttggagctgggggactcggccctttatctttgcgccagcgcttgc SEQ ID NO: 1285 TRBV5-2*01-5′ gaggctggaatcacccaagctccaagacacctgatcaaaacaagagaccagcaagtgacactgagatgctcccctgcctctgggcataactgtgtgtcct SEQ ID NO: 1286 TRBV5-2*01-3′ aacttgcctatgattctcagctcaccacgtccataactattactgagtcaaacacggagctaggggactcagccctgtatctctgtgccagcaacttg SEQ ID NO: 1287 TRBV5-3*01-5′ gaggctggagtcacccaaagtcccacacacctgatcaaaacgagaggacagcaagtgactctgagatgctctcctatctctgggcacagcagtgtgtcct SEQ ID NO: 1288 TRBV5-3*01-3′ cgattctcagggcgccagttccatgactgttgctctgagatgaatgtgagtgccttggagctgggggactcggccctgtatctctgtgccagaagcttgg SEQ ID NO: 1289 TRBV5-3*02-5′ gaggctggagtcacccaaagtcccacacacctgattaaaacgagaggacagcaagtgactctgagatgctctcctatctctgggcacagcagtgtgtcct SEQ ID NO: 1290 TRBV5-3*02-3′ cgattctcagggcgccagttccatgactattgctctgagatgaatgtgagtgccttggagctgggggactcggccctgtatctctgtgccagaagcttgg SEQ ID NO: 1291 TRBV5-4*01-5′ gagactggagtcacccaagtcccacacacctgatcaaaacgagaggacagcaagtgactctgagatgctcttctcagtctgggcacaacactgtgtcct SEQ ID NO: 1292 TRBV5-4*01-3′ agattctcaggtctccagttccctaattatagctctgagctgaatgtgaacgccttggagctggacgactcggccctgtatctctgtgccagcagcttgg SEQ ID NO: 1293 TRBV5-4*02-5′ gagactggagtcacccaaagtcccacacacctgatcaaaacgagaggacagcaagtgactctgagatgctcttctcagtctgggcacaacactgtgtcct SEQ ID NO: 1294 TRBV5-4*02-3′ tcctagattctcaggtctccagttccctaattataactctgagctgaatgtgaacgccttggagctggacgactcggccctgtatctctgtgccagcagc SEQ ID NO: 1295 TRBV5-4*03-5′ cagcaagtgacactgagatgctcttctcagtctgggcacaacactgtgcctggtaccaacaggccctgggtcaggggccccagtttatctttcagtatt SEQ ID NO: 1296 TRBV5-4*03-3′ tcctagattctcaggtctccagttccctaattatagctctgagctgaatgtgaacgccttggagctggacgactcggccctgtatctctgtgccagcagc SEQ ID NO: 1297 TRBV5-4*04-5′ actgtgtcctggtaccaacaggccctgggtcaggggccccagtttatctttcagtattatagggaggaagagaatggcagaggaaactcccctcctagat SEQ ID NO: 1298 TRBV5-4*04-3′ tcctagattctcaggtctccagttccctaattatagctctgagctgaatgtgaacgccttggagctggacgactcggccctgtatctctgtgccagcagc SEQ ID NO: 1299 TRBV5-5*01-5′ gacgctggagtcacccaaagtcccacacacctgatcaaaacgagaggacagcaagtgactctgagatgctctcctatctctgggcacaagagtgtgtcct SEQ ID NO: 1300 TRBV5-5*01-3′ cgattctcagctcgccagttccctaactatagctctgagctgaatgtgaacgccttgttgctgggggactcggccctgtatctctgtgccagcagcttgg SEQ ID NO: 1301 TRBV5-5*02-5′ gacgctggagtcacccaaagtcccacacacctgatcaaaacgagaggacagcacgtgactctgagatgctctcctatctctgggcacaagagtgtgtcct SEQ ID NO: 1302 TRBV5-5*02-3′ tgatcgattctcagctcgccagttccctaactatagctctgagctgaatgtgaacgccttgttgctgggggactcggccctgtatctctgtgccagcagc SEQ ID NO: 1303 TRBV5-5*03-5′ gacgctggagtcatccaaagtcccacacacctgatcaaaacgagaggacagcaagtgactctgagatgctctcctatctctgagcacaagagtgtgtcct SEQ ID NO: 1304 TRBV5-5*03-3′ tgatcgattctcagctcgccagttccctaactatagctctgagctgaatgtgaacgccttgttgctgggggactcggccctgtatctctgtgccagcagt SEQ ID NO: 1305 TRBV5-6*01-5′ gacgctggagtcacccaaagtcccacacacctgatcaaaacgagaggacagcaagtgactctgagatgctctccttagtctgggcatgacactgtgtcct SEQ ID NO: 1306 TRBV5-6*01-3′ cgattctcaggtcaccagttccctaactaatagctctgagctgaatgtgaacgccttgttgctgggggactcggccctctatctctgtgccagcagcttgg SEQ ID NO: 1307 TRBV5-7*01-5′ gatgctggagtcacccaaagtcccacacacctgatcaaaacgagaggacagcacgtgactctgagatgctctcctatctctgggcataccagtgtgtcct SEQ ID NO: 1308 TRBV5-7*01-3′ caattctcaggtcatcagttccctaactatagctctgagctgaatgtgaacgccttgttgctaggggactcggccctctatctctgtgccagcagcttgg SEQ ID NO: 1309 TRBV5-8*01-5′ gaggctggagtcacacaaagtcccacacacctgatcaaaacgagaggacagcaagcgactctgagatgctctcctatctctgggcacaccagtgtgtact SEQ ID NO: 1310 TRBV5-8*01-3′ agattttcaggtcgccagttccctaattatagctctgagctgaatgtgaacgccttggagctggaggactcggccctgtatctctgtgccagcagcttgg SEQ ID NO: 1311 TRBV5-8*02-5′ aggacagcaagcgactctgagatgctctcctatctctgggcacaccagtgtgtactggtaccaacaggccctgggtctgggcctccagctcctcctttgg SEQ ID NO: 1312 TRBV5-8*02-3′ tcctagattttcaggtcgccagttccctaattatagctctgagctgaatgtgaacgccttggagctggaggactcggccctgtatctctgtgccagcagc SEQ ID NO: 1313 TRBV6-1*01-5′ aatgctggtg6cactcagaccccaaaattccaggtcctgaagacaggacagagcatgacactgcagtgtgcccaggatatgaaccataactccatgtact SEQ ID NO: 1314 TRBV6-1*01-3′ gctacaatgtctccagattaaacaaacgggagttctcgctcaggctggagtcggctgctccctcccagacatctgtgtacttctgtgccagcagtgaagc SEQ ID NO: 1315 TRBV6-2*01-5′ aatgctggtgtcactcagaccccaaaattccgggtcctgaagacaggacagagcatgacactgctgtgtgcccaggatatgaaccatgaatacatgtact SEQ ID NO: 1316 TRBV6-2*01-3′ gctacaatgtctccagattaaaaaaacagaatttcctgctggggttggagtcggctgctccctcccaaacatctgtgtacttctgtgccagcagttactc SEQ ID NO: 1317 TRBV6-2*02-5′ aatgctggtgtcactcagaccccaaaattccgggtcctgaagacaggacagagcatgacactgctgtgtgcccaggatatgaaccatgaataccatgtact SEQ ID NO: 1318 TRBV6-2*02-3′ tggctacaatgtctccagattaaaaaaacagaatttcctgctggggttggagtcggctgctccctcccaaacatctgtgtacttctgtgccagcagccct SEQ ID NO: 1319 TRBV6-3*01-5′ aatgctggtgtcactcagaccccaaaattccgggtcctgaagacaggacagagcatgacactgctgtgtgcccaggatatgaaccatgaatacatgtact SEQ ID NO: 1320 TRBV6-3*01-3′ gctacaatgtctccagattaaaaaaacagaatttcctgctggggttggagtcggctgctccctcccaaacatctgtgtacttctgtgccagcagttactc SEQ ID NO: 1321 TRBV6-4*01-5′ attgctgggatcacccaggcaccaacatctcagatcctggcagcaggacggcgcatgacactgagatgtacccaggatatgagacataatgccatgtact SEQ ID NO: 1322 TRBV6-4*01-3′ gttatagtgtctccagagcaaacacagatgatttccccctcacgttggcgtctgctgtaccctctcagacatctgtgtacttctgtgccagcagtgactc SEQ ID NO: 1323 TRBV6-4*02-5′ actgctgggatcacccaggcaccaacatctcagatcctggcagcaggacggagcatgacactgagatgtacccaggatatgagacataatgccatgtact SEQ ID NO: 1324 TRBV6-4*02-3′ gttatagtgtctccagagcaaacacagatgatttccccctcacgttggcgtctgctgtaccctctcagacatctgtgtacttctgtgccagcagtgactc SEQ ID NO: 1325 TRBV6-4*01-5′ aatgctggtgtcactcagaccccaaaattccaggtcctgaagacaggacagagcatgacactgcagtgtgcccaggatatgaaccatgaatacatgtcct SEQ ID NO: 1326 TRBV6-4*01-3′ gctacaatgtctccagatcaaccacagaggatttcccgctcaggctgctgtcggctgctccctcccagacatctgtgtacttctgtgccagcagttactc SEQ ID NO: 1327 TRBV6-6*01-5′ aatgctggtgtcactcagaccccaaaattccgcatcctgaagataggacagagcatgacactgcagtgtacccaggatatgaaccataactacatgtact SEQ ID NO: 1328 TRBV6-6*01-3′ gctacaacgtctccagatcaaccacagaggatttcccgctcaggctggagttggctgctccctcccagacatctgtgtacttctgtgccagcagttactc SEQ ID NO: 1329 TRBV6-6*02-5′ aatgctggtgtcactcagaccccaaaattccgcatcctgaagataggacagagcatgacactgcagtgtgcccaggatatgaaccataactacatgtact SEQ ID NO: 1330 TRBV6-6*02-3′ gaatggctacaacgtctccagatcaaccacagaggatttccgctcaggctggagttggctgctccctcccagacatctgtgtacttctgtgccagcagt SEQ ID NO: 1331 TRBV6-6*03-5′ aatgctggtgtcactcagaccccaaaattccgcatcctgaagataggacagagcatgacactgcagtgtgcccaggatatgaaccataactacatgtact SEQ ID NO: 1332 TRBV6-6*03-3′ gaatggctacaacgtctccagatcaaccacagaggatttcccgctcaggctggagttggctgctccctcccagacatctgtgtacttctgtgccagcagt SEQ ID NO: 1333 TRBV6-6*04-5′ aatgctggtgtcactcagaccccaaaattccgcatcctgaagataggacagagcatgacactgcagtgtacccaggatatgaaccatgaatacatgtact SEQ ID NO: 1334 TRBV6-6*04-3′ tggctacaatgtctccagatcaaccacagaggatttcccgctcaggctggagttggctgctccctcccagacatctgtgtacttctgtgccagcagtcga SEQ ID NO: 1335 TRBV6-6*05-5′ aatgctggtgtcactcagaccccaaaattccgcatcctgaagataggacagagcatvgacactgcagtgtgcccaggatatgaaccataactacatgtact SEQ ID NO: 1336 TRBV6-6*05-3′ gaatggctacaacgtctccagatcaaccacagaggatttcccgctcaggctggagttggctgctgcctcccagacatctgtgtacttctgtgccagcagc SEQ ID NO: 1337 TRBV6-7*01-5′ aatgctggtgtcactcagaccccaaaattccacgtcctgaagacaggacagagcatgactctgctgtgtgcccaggatatgaaccatgaatacatgtatc SEQ ID NO: 1338 TRBV6-7*01-3′ gctacaatgtctccagatcaaacacagaggatttccccctcaagctggagtcagctgctccctctcagacttctgtttacttctgtgccagcagttactc SEQ ID NO: 1339 TRBV6-8*01-5′ aatgctggtgtcactcagaccccaaaattccacatcctgaagacaggacagagcatgacactgcagtgtgccaggatatgaaccatggatacatgtcct SEQ ID NO: 1340 TRBV6-8*01-3′ gctacaatgtctctagattaaacacagaggatttcccactcaggctggtgtcggctgctccctcccagacatctgtgtacttgtgtgccagcagttactc SEQ ID NO: 1341 TRBV6-9*01-5′ aatgctggtgtcactcagaccccaaaattccacatcctgaagacaggacagagcatgacactgcagtgtgcccaggatatgaaccatggatacttgtcct SEQ ID NO: 1342 TRBV6-9*01-3′ gctacaatgtatccagatcaaacacagaggatttcccgctcaggctggagtcagctgctccctcccagacatctgtatacttctgtgccagcagttattc SEQ ID NO: 1343 TRBV7-1*01-5′ ggtgctggagtctcccagtccctgagacacaaggtagcaaagaagggaaaggatgtagctctcagataatgatccaatttcaggtcataatgccctttatt SEQ ID NO: 1344 TRBV7-1*01-3′ ggttctctgcacagaggtctgagggatccatctccactctgaagttccagcgcacatagcagggggacttggctgtgtatctctgtgccagcagctcag SEQ ID NO: 1345 TRBV7-2*01-5′ ggagctggagtctcccagtcccccagtaacaaggtcacagagaagggaaaggatgtagagctcaggtgtgatccaatttcaggtcatactgccctttact SEQ ID NO: 1346 TRBV7-2*01-3′ gcttctctgcagagaggactgggggatccgtctccactctgacgatccagcgcacacagcaggaggactcggccgtgtatctcgtgccagcagcttagc SEQ ID NO: 1347 TRBV7-2*02-5′ ggagctggagtctcccagtcccccagtaacaaggtcacagagaagggaaaggatgtagagctcaggtgtgatccaatttcaggtcatactgccctttact SEQ ID NO: 1348 TRBV7-2*02-3′ gcttctctgcagagaggactggggaatccgtctccactctgacgatccagcgcacacagcaggaggactcggccgtgtatctctgtgccagcagcttagc SEQ ID NO: 1349 TRBV702*03-5′ ggagctggagtctcccagtcccccagtaacaaggtcacagagaagggaaaggatgtagagctcaggtgtgatccaatttcaggtcatactgccctttact SEQ ID NO: 1350 TRBV7-2*03-3′ gcttctctgcagagaggactggggaatccgtctccactctgacgatccagcgcacacagcaggaggactcggccgtgtatctctgtaccagcagcttagc SEQ ID NO: 1351 TRBV7-2*04-5′ ggagctggagtttcccagtcccccagtaacaaggtcacagagaagggaaaggatgtagagctcaggtgtgatccaatttcaggtcatactgccctttact SEQ ID NO: 1352 TRBV702*04-3′ tcgcttctctgcagagaggactgggggatccgtctccactctgacgatccagcgcacacagcaggaggactcggccgtgtatctctgtgccagcagctta SEQ ID NO: 1353 TRBV7-3*01-5′ ggtgctggagtctcccagacccccagtaacaaggtcacagagaagggaaaatatgtagagctcaggtgtgatccaatttcaggtcatactgccctttact SEQ ID NO: 1354 TRBV7-3*01-3′ ggttctttgcagtcaggcctgagggatccgtctctactctgaagatccagcgcacagagcggggggactcagccgtgtatctctgtgccagcagcttaac SEQ ID NO: 1355 TRBV7-3*02-5′ ggtgctggagtctcccagacccccagtaacaaggtcacagagaagggaaaagatgtagagctcaggtgtgatccaatttcaggtcatactgccctttact SEQ ID NO: 1356 TRBV7-3*02-3′ ggttctttgcagtcaggcctgagggatccgtctctactctgaagatccagcgcacagagcagggggactcagccgtgtatctccgtgccagcagcttaac SEQ ID NO: 1357 TRBV7-3*03-5′ ggtgctggagtctcccagacccccagtaacaaggtcacagagaagggaaaagatgtagagctcaggtgtgatccaatttcaggtcatactgccctttact SEQ ID NO: 1358 TRBV7-3*03-3′ ggttctttgcagtcaggcctgagggatccgtctctactctgaagatccagcgcacagagcagggggactcagccgcgtatctccgtgccagcagcttaac SEQ ID NO: 1359 TRBV7-3*04-5′ ggtgctggagtctcccagacccccagtaacaaggtcacagagaagggaaaatatgtagagctcaggtgtgatccaatttcaggtcatactgccctttact SEQ ID NO: 1360 TRBV7-3*04-3′ cgatcggttctttgcagtcaggcctgagggatccgtctctactctgaagatccagcgcacagagcggggggactctgccgtgtatctctgtgccagcagc SEQ ID NO: 1361 TRBV7-3*05-5′ tgggagctcaggtgtgatccaatttcaggtcatactgccctttactggtaccgacaaagcctggggcagggcccagagcttctaatttacttccaaggca SEQ ID NO: 1362 TRBV7-3*05-3′ tgatcggttctttgcagtcaggcctgagggatccgtctctactctgaagatccagcgcacagagcggggggactcagccgtgtatctctgtgccagcagc SEQ ID NO: 1363 TRBV7-4*01-5′ ggtgctggagtctcccagtccccaaggtacaaagtcgcaaagaggggacgggatgtagctctcaggtgtgattcaatttcgggtcatgtaaccctttatt SEQ ID NO: 1364 TRBV7-4*01-3′ ggttctctgcagagaggcctgagagatccgtctccactctgaagatccagcgcacagagcagggggactcagctgtgtatctctgtgccagcagttagc SEQ ID NO: 1365 TRBV7-4*02-5′ ggtgctggagtcctcccagtccccaaggtacaaagtcgcaaagaggggacgggatgtagctctcaggtgtgattcaatttcgggtcatgtaaccctttatt SEQ ID NO: 1366 TRBV7-4*02-3′ aacgagacaaatcagggcggcccagtggtcggttctctgcagagaggcctgagagatcgtctccactccgaagatccagcgcacagagcagggggactca SEQ ID NO: 1367 TRBV7-5*01-5′ ggtgctggagtctcccagtccccaaggtacgaagtcacacagaggggacaggatgtagctcccaggtgtgatccaatttcgggtcaggtaaccctttatt SEQ ID NO: 1368 TRBV7-5*01-3′ tcattctccacagagaggtctgaggatcttctccacctgaagatccagcgcacagagcaagggcgactcggctgtgtatctctgtgccagaagcttag SEQ ID NO: 1369 TRBV7-5*02-5′ ggtgctggagtctcccagtccccaaggtacgaagtcacacagaggggacaggatgtagctcccaggtgtgatccaatttcgggtcaggtaaccctttatt SEQ ID NO: 1370 TRBV7-5*02-3′ caattctccacagagaggtctgaggatctttctccacctgaagatccagcgcacagagtaagggcgactcggctgtgtatctctgtgcagaagcttagc SEQ ID NO: 1371 TRBV7-6*01-5′ ggtgctggagtctcccagtctcccaggtacaaagtcacaaagaggggacaggatgtagctctcaggtgtgatccaatttcgggtcatgtatccctttatt SEQ ID NO: 1372 TRBV7-3*01-3′ ggttctctgcagagaggcctgagggatccatctccactctgacgatccagcgcacagagcagcgggactcggccatgtatcgctgtgccagcagcttagc SEQ ID NO: 1373 TRBV7-6*02-5′ ggtgctggagtctcccagtctcccaggtacaaagtcacaaagaggggacaggatgtagctctcaggtgtgatccaatctcgggtcatgtatccctttatt SEQ ID NO: 1374 TRBV7-6*02-3′ tgatcggttctctgcagagaggcctgagggatccatctccactctgacgatccagcgcacagagcagcgggactcggccatgtatcgctgtgccagcagc SEQ ID NO: 1375 TRBV7-7*01-5′ ggtgctggagtctcccagtctcccaggtacaaagtcacaaagaggggacaggatgtaactctcaggtgtgatccaatttcgagtcatgcaaccctttatt SEQ ID NO: 1376 TRBV7-7*01-3′ ggttctctgcagagaggcctgagggatccatctccactctgatgattcagcgcacagagcagcgggactcagccatgtatcgctgtgccagcagcttagc SEQ ID NO: 1377 TRBV7-7*02-5′ ggtgctggagtctcccagtctcccaggtacaaagtcacaaagaggggacaggatgtaactctcaggtgtgatccaatttcgagtcatgtaaccctttatt SEQ ID NO: 1378 TRBV7-7*02-3′ tgatcggttctctgcagagaggcctgagggatccatctcactctgacgattcagcgcacagagcagcgggactcagccatgtatcgctgtgccagcagc SEQ ID NO: 1379 TRBV7-8*01-5′ ggtgctggagtctcccagtcccctaggtacaaagtcgcaaagagaggacaggatgtagctctcaggtgtgatccaatttcgggtcatgtatcccttttt SEQ ID NO: 1380 TRBV7-8*01-3′ gcttcttgcagaaaggcctgagggatccgtctccactctgaagatccagcgcacacagcaggaggactccgccgtgtatctctgtgccagcagcttagc SEQ ID NO: 1381 TRBV7-8*02-5′ ggtgctggagtctcccagtcccctaggtacaaagtcgcaaagagaggacaggatgtagctctcaggtgtgatccaatttcgggtcatgtatcccttttt SEQ ID NO: 1382 TRBV7-8*02-3′ gcttctttgcagaaaggcctgagggatccgtctccactctgaagatccagcgcacacagaaggaggactccgccgtgtatctctgtgccagcagcttagc SEQ ID NO: 1383 TRBV7-8*03-5′ ggtgctggagtctcccagtcccctaggtacaaagtcgcaaagagaggacaggaatgtagctctcaggtgtgatccaatttcgggtcatgtatcccttttt SEQ ID NO: 1384 TRBV7-8*03-3′ tcgcttctttgcagaaaggcctgagggatccgtctccactcgaagatccagcgcacacagcaggaggactccgccgtgtatctctgtgccagcagccga SEQ ID NO: 1385 TRBV7-9*01-5′ gatactggagtctcccagaaccccagacacaagatcacaaagaggggacagaatgtaactttcaggtgtgatccaatttctgaacacaaccgcctttatt SEQ ID NO: 1386 TRBV7-9*01-3′ ggttctctgcagagaggcctaagggatctttctccaccttggagatccagcgcacagagcagggggactcggccatgtatctctgtgccagcagcttagc SEQ ID NO: 1387 TRBV7-9*02-5′ gatactggagtctcccagaaccccagacacaacatcacaaagaggggacagaatgtaactttcaggtgtgatccaatttctgaacacaaccgcctttatt SEQ ID NO: 1388 TRBV7-9*02-3′ tcggttctctgcagagaggcctaagggatctttctccaccttggagatccagcgcacagagcagggggactcggccatgtatctctgtgccagcagctta SEQ ID NO: 1389 TRBV7-9*03-5′ gatactggagtctcccaggaccccagacacaagatcacaaagaggggacagaatgtaactttcaggtgtgatccaatttctgaacacaaccgcctttatt SEQ ID NO: 1390 TRBV7-9*03-3′ tgatcggttctctgcagagaggcctaagggatctttctccaccttggagatccagcgcacagagcagggggactcggccatgtatctctgtgccagcagc SEQ ID NO: 1391 TRBV7-9*04-5′ atatctggagtctcccacaaccccagacacaagatcacaaagaggggacagaatgtaactttcaggtgtgatccaatttctgaacacaacgcctttatt SEQ ID NO: 1392 TRBV7-9*04-3′ tcggatctctgcagagaggcctaagggatctttctccaccttggagatccagcgcacagagcagggggactcggccatgtatctctgtgccagcagctct SEQ ID NO: 1393 TRBV7-9*05-5′ gatactggagtctcccagaaccccagacacaagatcacaaagaggggacagaatgtaactttcaggtgtgatccaatttctgaacacaaccgcctttatt SEQ ID NO: 1394 TRBV7-9*05-3′ tcggttctctgcagagaggcctaagggatctctctccaccttggagatccagcgcacagagcagggggactcggccatgtatctctgtgccagcaccaaa SEQ ID NO: 1395 TRBV7-9*06-5′ gatactggagtctcccagaaccccagacacaagatcacaaagaggggacagaatgtaactttcaggtgtgatccaatttctgaacacaaaccgcctttatt SEQ ID NO: 1396 TRBV7-9*06-3′ tcggttctctgcagagaggcctaagggatctctttccaccttggagatccagcgcacagagcaggggactcggccatgtatctctgtgccagcacgttg SEQ ID NO: 1397 TRBV7-9*07-5′ cacaaccgcctttattggtaccgacagaccctggggcagggcccagagtttctgacttacttccagaatgaagctcaactagaaaaatcaaggctgctca SEQ ID NO: 1398 TRBV7-9*07-3′ gttctctgcagagaggcctaagggatctttctccaccttggagatccagcgcacagaggagggggactcggccatgtatctctgtgccagcagcagcagt SEQ ID NO: 1399 TRBV8-1*01-5′ gaggcagggatcagccagataccaagatatcacagacacacagggaaaaagatcatcctgaaatatgctcagattaggaaccattattcagtgttctgtt SEQ ID NO: 1400 TRBV8-1*01-3′ ggaagggtacaatgtctctggaaacaagctcaagcattttccctcaaccctggagtctactagcaccagccagacctctgtacctctgtggcagtgcatc SEQ ID NO: 1401 TRBV8-2*01-5′ gatgctgggatcacccagatgccaagatatcacattgtacagaagaaagagatgatcctggaatgtgctcaggttaggaacagtgttctgatatcgacag SEQ ID NO: 1402 TRBV8-2*01-3′ agaggggtactgtgtttcttgaaacaagcttgagcatttccccaatcctggcatccaccagcaccagccagacctaatctgtaccactgtggcagcacatc SEQ ID NO: 1403 TRBV9*01-5′ gattctggagtcacacaaaccccaaagcacctgatcacagcaactggacagcgagtgacgctgagatgctcccctaggtctggagcctctctgtgtact SEQ ID NO: 1404 TRBV9*01-3′ cgattctccgcacaacagttccctgacttgcactctgaactaaacctgagctctctggagctgggggactcagctttgtatttctgtgccagcagcgtag SEQ ID NO: 1405 TRBV9*02-5′ gattctggagtcacacaaaccccaaagcacctgatcacagcaactggacagcgagtgacgctgagatgctcccctaggtctggagacctctctgtgtact SEQ ID NO: 1406 TRBV9*02-3′ cgattctccgcacaacagttccctgacttgcactctgaactaaacctgagctctctggagctgggggactcagctttgtatttctgtgccagcagcgtag SEQ ID NO: 1407 TRBV9*03-5′ gattctggagtcacacaaaccccaaagcacctgatcacagcaactggacagcgagtgacgttgagatgctcccctaggtctggagacctctctgtgtact SEQ ID NO: 1408 TRBV9*03-3′ tgaatgattctccgcataacagttccctgacttgcactcgaactaaacctgagctctctggagctgggggactcagctttgtatttctgtgccagcagc SEQ ID NO: 1409 TRBVA*01-5′ gaagctgaagccacctagactctaagacacctgattgcagagacaggaaaggagttctcaagataagtgccaagatttcatactggttttcacaagaatc SEQ ID NO: 1410 TRBVA*01-3′ tccctattgaaaatatttcctggcaaaaaatagaagttctctttggctcgaaatctgcaactccctttcaggtgtccctgtgccttgtaccgtcactc SEQ ID NO: 1411 TRBVA/OR9-2*01- gaagctgaagtcacctagactccaagacacctgattgtagagacaggaaaggagttctcaggatatgtgccataatttcatactggtttctacaagaatc 5′ SEQ ID NO: 1412 TRBVA/OR9-2*01- tccctgttgaaaatatttcccggcaaaaaacagaagttccctttggctctgaaatctgcaaagccctttcagatgtccctgtgtccttgtgccgtcactc 3′ SEQ ID NO: 1413 TRBVB*01-5′ aatgtcaaagtaacacagaccctgagatgaggcaggaaagttgtatcggaatgttttcagactatcaaccagaccaaacgttctggaatccataagatcc SEQ ID NO: 1414 TRBVB*01-3′ gactctgagaccctctgcagcagcagcctatcagtgcagccacatcctctctgagcggatatgacaaaccccagggttgaagcgacctaacctatgagcc SEQ ID NO: 1415 TRBVC*01-5′ agtgacttctaaattggtctatgaagagaatctcccccattcctggagtcgcccagtccagacctctctgtacatttgcaccagcagtttatccacagt SEQ ID NO: 1416 TRDV1*01-5′ gcccagaaggttactcaagcccagtcatcagtatccatgccagtgaggaaagcagtcaccctgaactgcctgtatgaaacaagttggtggtcatattata SEQ ID NO: 1417 TRDV1*01-3′ attctgtcaacttcaagaaagcagcgaaatccgtcgccttaaccatttcagccttacagctagaagattcagcaaagtactttgtgctcttggggaact SEQ ID NO: 1418 TRDV2*01-5′ gccattgagttggtgcctgaacaccaaacagtgcctgtgtcaataggggtccctgccaccctcaggtgctccatgaaggagaagcgatcggtaactact SEQ ID NO: 1419 TRDV2*01-3′ tttccaaggtgacattgatattgcaaagaacctggctgtacttaagatacttgcaccatcagagagagatgaagggtcttactactgtgcctgtgacacc SEQ ID NO: 1420 TRDV2*02-5′ attgagttggtgcctgaacaccaaacagtgcctgtgtcaatagggatccctgccaccctcaggtgctccatgaaaggagaagcgatcggtaactactata SEQ ID NO: 1421 TRDV2*02-3′ aatttccaaggtgacattgatattgcaaagaacctggctgacttaagatacttgcaccatcagagagagatgaagggtcttactactgtgcctgtgaca SEQ ID NO: 1422 TRDV2*03-5′ gccattgagttggtgcctgaacaccaaacagtgcctgtgtcaataggggtccctgccaccctcaggtgctccatgaaggagaagcgatcggtaactact SEQ ID NO: 1423 TRDV2*03-3′ tttccaaggtgacattgatattgcaaagaacctggctgtacttaagatacttgcaccatcagagagagatgaagggtcttactactgtgcctgtgacacc SEQ ID NO: 1424 TRDV3*01-5′ tgtgacaaagtaacccagagttccccggaccagacggtggcgagtggcagtgaggtggtactgctctgcacttacgacactgtatattcaaatccagatt SEQ ID NO: 1425 TRDV3*01-3′ gacggttttctgtgaaacacattctgacccagaaagcctttcacttggtgatctctccagtaaggactgaagacagtgccacttactactgtgcctttag SEQ ID NO: 1426 TRDV3*02-5′ tgtgacaaagtaacccagagttccccggaccagacggtggcgagtggcagtgaggtggtactgctctgcacttacgacactgtatattcaaatccagatt SEQ ID NO: 1427 TRDV3*02-3′ gacggttttctgtgaaacacattctgacccagaaagcctttcacttggtgatctctccagtaaggactgaagacagtgccacttactactgtgcctttag SEQ ID NO: 1428 TRGV1*01-5′ tcttccaacttggaagggagaacgaagtcagtcaccaggctgactgggtcatctgctgaaatcacctgtgatcttcctggagcaagtaccttatacatcc SEQ ID NO: 1429 TRGV1*01-3′ aaagtatgacactggaagcacaaggagcaattggaatttgagactgcaaaatctaattaaaaatgattctgggttctattactgtgccacctgggacagg SEQ ID NO: 1430 TRGV10*01-5′ ttatcaaaagtggagcagttccagctatccatttccacggaagtcaagaaaagtattgacataccttgcaagatatcgagcacaaggtttgaaacagatg SEQ ID NO: 1431 TRGV10*01-3′ aggcaagaaagaattctcaaactctcacttcaatccttaccatcaagtccgtagagaaagaagacatggccgtttactactgtgctgcgtggtgggtggc SEQ ID NO: 1432 TRGV10*02-5′ ttatcaaaagtggagcagttccagctatccatttccacggaagtcaagaaaagtattgacataccttgcaagatatcgagcacaaggtttgaaacagatg SEQ ID NO: 1433 TRGV10*02-3′ tggaggcaagaaagaattctcaaactctcacttcaatccttaccatcaagtccgtagagaaagaagacatggccgtttactactgtgctgcgtgggatta SEQ ID NO: 1434 TRGV11*01-5′ cttgggcagttggaacaacctgaaatatctatttccagaccagcaaataagagtgcccacatatcttggaaggcatccatccaaggctttagcagtaaaa SEQ ID NO: 1435 TRGV11*01-3′ ggtaagtaaaaatgctcacacttccacttccactttgaaaataaagttcttagagaaagaagatgaggtggtgtaccactgtgcctgctggattaggcac SEQ ID NO: 1436 TRGV11*02-5′ cttgggcagttggaacaacctgaaatatctatttccagaccagcaaataagagtgcccacatatcttggaaggcatccaatccaaggctttagcagtaaaa SEQ ID NO: 1437 TRGV11*02-3′ gataagtaaaaatgctcacacttccacttccactttgaaaataaagttcttagagaaagaagatgaggtggtgtaccactgtgcctgctggattaggcac SEQ ID NO: 1438 TRGV2*01-5′ tcttccaacttggaagggagaacgaagtcagtcatcaggcagactgggtcatctgctgaaatcacttgtgatcttgctgaaggaagtaacggctacatcc SEQ ID NO: 1439 TRGV2*01-3′ gtattatacttacgcaagcacaaggaacaacttgagattgatactgcgaaatctaattgaaaatgactctggggtctattactgtgccacctgggacggg SEQ ID NO: 1440 TRGV2*02-5′ tcttccaacttggaagggagaacgaagtcagtcatcaggcagactgggtcatctgctgaaatcacttgtgatcttgctgaaggaagtaacggctacatcc SEQ ID NO: 1441 TRGV2*02-3′ gaagtattatacttacgcaagcacaaggaacaacttgagattgatactgcaaaatctaattgaaaatgactctggggtctattactgtgccacctgggac SEQ ID NO: 1442 TRGV3*01-5′ tcttccaacttggaagggagaacgaagtcagtcaccaggcagactgggtcatctgctgaaatcacttgcgatcttactgtaacaaataccttctacatcc SEQ ID NO: 1443 TRGV3*01-3′ gtattatactcatacacccaggaggtggagctggatattgagactgcaaaatctaattgaaatgattctggggtctattactgtgccacctgggacagg SEQ ID NO: 1444 TRGV3*02-5′ tcttccaacttggaagggagaacgaagtcagtcaccaggcagactgggtcatctgctgaaatcaccttgcgatcttactgtaacaaataccttctacatcc SEQ ID NO: 1445 TRGV3*02-3′ agtattatactcatacacccaggaggtggagctggatattgagactgcaaaatctaattgaaaatgattctggggtctattactgtgccacctgggacag SEQ ID NO: 1446 TRGV4*01-5′ tcttccaacttggaagggagaacgaagtcagtcatcaggcagactgggtcatctgctgaaatcacttgtgatcttgctgaaggaagtaccggctacatcc SEQ ID NO: 1447 TRGV4*01-3′ gtatgatacttatggaagcacaaggaagaacttgagaatgatactgcgaaatcttattgaaaatgactctggagtctattactgtgccacctgggatggg SEQ ID NO: 1448 TRGV4*02-5′ tcttccaacttggaagggagaacgaagtcagtcatcaggcagactgggtcatctgctgaaatcacttgtgatcttgctgaaggaagtaccggctacatcc SEQ ID NO: 1449 TRGV4*02-3′ gtatgatacttacggaagcacaaggaagaacttgagaatgatactgcgaaatcttattgaaaatgactctggagtctattactgtgccacctgggatggg SEQ ID NO: 1450 TRGV5*01-5′ tcttccaacttggaagggggaacgaagtcagtcatgaggccgactaggtcatctgctgaaatcacttgtgaccttactgtaataaatgccttctacatcc SEQ ID NO: 1451 TRGV5*01-3′ gtattatactcatacacccaggaggtggagctggatattgatactacgaaatctaattgaaaatgattctggggctattactgtgccacctgggacagg SEQ ID NO: 1452 TRGV5P*01-5′ tcttccaacttggaagggagaatgaagtcagtcaccaggccgactgggtcatctgctgaaatcacttgtgaccttactgtaataaatgccgtctacatcc SEQ ID NO: 1453 TRGV5P*01-3′ gtattatactcatacaccgaggaggtggagctggaatttgagactgcaaaatctaattgaaaatgattctggggtctattactgtgccacctggggcagg SEQ ID NO: 1454 TRGV5P*02-5′ tcttccaacttggaagggagaatgaagtcagtcaccaggccgactgggtcatctgctgaaatcacttgtgaccttactgtaataaatgccgtctacatcc SEQ ID NO: 1455 TRGV5P*02-3′ gtattatactcatacaccgaggaggtggagctggaatttgagactgcaaaatctattgaaaatgattctggggtctattactgtgccacctggggcagg SEQ ID NO: 1456 TRGV6*01-5′ tctactaacttggaagcgaaaataaagtcaggcaccaggcagatggggtcatctgctgtaatcacctgtgatcttcctgtagaaaatgccttctacatcc SEQ ID NO: 1457 TRGV6*01-3′ gcatgatacttatggaagtagaaggataagctggaaatttatacctccaaactaaatgaaaatgcctctggggttattactgtgccacctaggacagg SEQ ID NO: 1458 TRGV6*02-5′ tctactaacttggaagcgaaaataaagtcaggcaccaggcagatggggtcatctgctgtaatcacctgtgatcttcctgtagaaaatgccttctacatcc SEQ ID NO: 1459 TRGV6*02-3′ gcatgatacttatggaagtagaaggataagctggaaatttatacctccaaaacctaaatgaaaatgcctctggggtctattactgtgccacctaggacagg SEQ ID NO: 1460 TRGV7*01-5′ tcttccaacttgcaagggagaaggaagtcagtcaccaggccagctgggtcatctgctgtaatcacttgtgatcttactgtaataaatacfcttctacatcc SEQ ID NO: 1461 TRGV7*01-3′ atattttacttatgcaagcatgaggaggagctggaaaattgatactgcaaaatctaattgaaaatgattctggatctattactgtgtccacctgggacagg SEQ ID NO: 1462 TRGV8*01-5′ tcttccaacttggaagggagaacaaagtcagtcaccaggccaactgggtcatcagctgtaatcacttgtgatcttcctgtagaaaatgccgtctacaccc SEQ ID NO: 1463 TRGV8*01-3′ gtatcatacttatgcaagcacagggaagagccttaaatttatactggaaaatctaattgaacgtgactctggggtctattactgtgccacctgggatagg SEQ ID NO: 1464 TRGV9*01-5′ gcaggtcacctagagcaacctcaaatttccagtactaaaacgctgtcaaaaacagcccgcctggaatgtgtggtgtctggaataacaatttctgcaacat SEQ ID NO: 1465 TRGV9*01-3′ tgaggtggataggatacctgaaacgtctacatccactctcaccattcacaatgtagagaaacaggacatagctacctactactgtgccttgtgggaggtg SEQ ID NO: 1466 TRGV9*02-5′ gcaggtcacctagagcaacctcaaatttccagtactaaaacgctgtcaaaaaccagcccgcctggaatgtgtggtgtctggaataaaaatttctgcaacat SEQ ID NO: 1467 TRGV9*02-3′ tgaggtggataggatacctgaaacgtctacatccactctcaccattcacaatgtagagaaacaggacatagctacctactactgtgccttgtgggaggtg SEQ ID NO: 1468 TRGVA*01-5′ ctcatcaggccggagcagctggcccatgtcctggggcactagggaagcttggtcatcctgcagtgcgtggtccgcaccaggatcagctacacccactggt SEQ ID NO: 1469 TRGVA*01-3′ agataaaatcatagccaaggatggcagcagctctatcttggcagtactgaagttggagacaggcatcgagggcatgaactactgcacaacctgggccctg SEQ ID NO: 1470 TRGVB*01-5′ tttaaagcaataaaaaatgtcaactacatttttgtcaacagagcaacagataaaaagtgtctaggtatcttgtgtggtgtccactgaagactttgtaaata SEQ ID NO: 1471 TRGVB*01-3′ cttgaggcaagaacaattttcaaatgtctacttcagtctttaccataaacttcataggaaaggaagatgaggccatttactactgcactgcttaggacc SEQ ID NO: 1472 TRAJ1*01 aatagagacacggggcatggtatgaaagtattacctcccagttgcaatttggcaaaggaaccagagtttccacttctccccgtacgtctgcccatgccca SEQ ID NO: 1473 TRAJ10*01 gaggcatcaaacactgtgatactcacgggaggaggaaacaaactcacctttgggacaggcactcagctaaaagtggaactcagtaagtatgagattctat SEQ ID NO: 1474 TRAJ11*01 tatggggatttgctatagtgtgaattcaggatacagcaccctcacctttgggaaggggactatgcttctagtctctccaggtacatgttgaccccatccc SEQ ID NO: 1475 TRAJ12*01 actgactaagaaacactgtgggatggatagcagctataaattgatcttcgggagtgggaccagactgctggtcaggcctggtaagtaaggtgtcagagag SEQ ID NO: 1476 TRAJ13*01 aagcaggcattacagtgtgaattctgggggttaccagaaagttacctttggaattggaacaaagctccaagtcatcccaagtgagtccaatttcctatg SEQ ID NO: 1477 TRAJ13*02 aaaggcaggcattacagtgtgaattctgggggttaccagaaagttacctttggaactggaacaaagctccaagtcatcccaagtgagtccaatttcctat SEQ ID NO: 1478 TRAJ14*01 tttgtcaggcagcacagtgctgtgatttatagcacattcatctttgggagtgggacaagattatcagtaaaacctggtaagtaggcaatatgtcactaaa SEQ ID NO: 1479 TRAJ15*01 cagggcctcatttcactgtgccaaccaggcaggaactgctctgatctttgggaagggaaccaccttatcagtgagttccagtaagtacctgataattatt SEQ ID NO: 1480 TRAJ15*02 cagggcctcatttcactgtgccaaccaggcaggaactgctctgatctttgggaagggaacccacctatcagtgagttccagtaagtaccgataattatt SEQ ID NO: 1481 TRAJ16*01 tggtacaatagatcactgtgggttttcagatggccagaagctgctctttgcaaggggaaccatgttaaaggtggatcttagtaagtattattactaatga SEQ ID NO: 1482 TRAJ17*01 cctgtggtttttgctgggccttaaatcattgtgtgatcaaagctgcaggcaacaagctaactttggaggaggaaccagggtgctagttaaaccaagtga SEQ ID NO: 1483 TRAJ18*01 aggggaccagcattgtgccgacagaggctcaaccctggggaggctatactttggaagaggaactcagttgactgtctggcctggtgagtgagtcgctttc SEQ ID NO: 1484 TRAJ19*01 ttttgcagaggacagatgtggctatcaaagattttacaatttcacctttggaaagggatccaaacataatgtcactccaagtaagtgagcagccttttgt SEQ ID NO: 1485 TRAJ2*01 tggtgtcacctacggtatgaatactggaggaacaattgataaactcacatttgggaaagggacccatgtattcattatatctggtgagtcatcccaggtg SEQ ID NO: 1486 TRAJ20*01 tgtaggcgacctcgcactgtggttctaacgactacaagctcagctttggagccggaaccacagtaactgtaagagcaagtaagtaagaaagaaaagtcca SEQ ID NO: 1487 TRAJ21*01 tgtaatgccaataaacatggtgtacaacttcaacaaattttactttggatctgggaccaaactcaatgtaaaaccaagtaagttatagttgcctagaaga SEQ ID NO: 1488 TRAJ22*01 gttgagcaaatcatagtgtttcttctggttctgcaaggcaactgacctttggatctgggacacaattgactgttttacctggtaggctgcctcaattaaa SEQ ID NO: 1489 TRAJ23*01 aggatatgtaacacagtgtgatttataaccagggaggaaagcttatcttcggacagggaacggagttatctgtgaaacccagtaagtataaaattgtatc SEQ ID NO: 1490 TRAJ23*02 gactggatgtgtttttgacaggatatgtaacacagtgtgatttataaccagggaggaaagcttatcttcggacagggaacggagctatctgtgaaaccca SEQ ID NO: 1491 TRAJ24*01 gaggtgtttgtcacagtgtgacaactgacagctgggggaaattcgagtttggagcagggacccaggttgtggtcaccccaggtaagcccattcctggagc SEQ ID NO: 1492 TRAJ24*02 gaggtgtttgtcacagtgtgacaactgacagctgggggaaattgcagtttggagcagggacccaggttgtggtcaccccaggtaagccccattccctgga SEQ ID NO: 1493 TRAJ25*01 atgctgagataatcactatgcagaaggacaaggcttctcctttatctttgggaaggggacaaggctgcttgtcaagccaagtaagtgacatataatttat SEQ ID NO: 1494 TRAJ26*01 ctgagcccagaaacacftgtggggataactatggtcagaattttgtctttggtcccggaaccagattgtccgtgctgccctgtaagtacagttaagtggag SEQ ID NO: 1495 TRAJ27*01 caatagcactaaagactgtgtaacaccaatgcaggcaaatcaacctttggggatgggactacgctcactgtgaagccaagtaagttgtgttcttctttgc SEQ ID NO: 1496 TRAJ28*01 agaaaggaaactctgtgcatactctggggctgggagttaccaactcactttcgggaaggggaccaaactctcggtcataccaagtaagttcttctttctg SEQ ID NO: 1497 TRAJ29*01 ttatggaggaaatcactgtgggaattcaggaaacacacctcttgtctttggaaagggcacaagactttctgtgattgcaagtaagtgtttctagccatcc SEQ ID NO: 1498 TRAJ3*01 aaagaccttacccacagtgggggtacagcagtgcttccaagataatctttggatcagggaccagactcagcatccggccaagtaagtagaatgaagcagg SEQ ID NO: 1499 TRAJ30*01 gttatggtcccaatcacagtgtgaacagagatgacaagatcatctttggaaaagggacacgacttcatattctccccagtaagtgctgtttatgtgattt SEQ ID NO: 1500 TRAJ31*01 agtaaaggcaggaagtgctgtggaataacaatgccagactcatgtttggagatggaactcagctggtggtgaagcccagtaagtggccatgttttattga SEQ ID NO: 1501 TRAJ32*01 ggctctgaaggactgtgtgaattatggcggtgctacaaacaagctcatctttggaactggcactctgcttgctgtccagccaagtacgtaagtagtggca SEQ ID NO: 1502 TRAJ32*02 gtgattcagccacctacctctgtgccgatggtggtgctacaaacaagctcatctttggaactggcactctgcttgctgtccagccaaatatccagaaccc SEQ ID NO: 1503 TRAJ33*01 gttaaggtttttgtgtctgtgtggatagcaactatcagttaatctggggcgctgggaccaagctaattataaagccaggtaagtctcagagatgtgactg SEQ ID NO: 1504 TRAJ34*01 aggtttttgtagatctcagtatcactgtgtcttataacaccgacaagctcatctttgggactgggaccagattacaagtctttccaagt SEQ ID NO: 1505 TRAJ35*01 taaaagaatgagccattgtggataggctttgggaatgtgctgcattgcgggtccggcactcaagtgattgtttaccacgtaagtatatcttttctcatt SEQ ID NO: 1506 TRAJ36*01 tactgggcagaaacactgtgtcaaactggggcaaacaacctcttctttgggactggaacgagactcaccgttattccctgtaagtccttacctcttgaca SEQ ID NO: 1507 TRAJ37*01 aaagtacagcattagagtgtggctctggcaacacaggcaaactaatctttgggcaagggacaactttacaagtaaaaccaggtaggtctggatgtttcca SEQ ID NO: 1508 TRAJ37*02 ctcagcggtgtacttctgtgctcttcatggctctagcaacacaggcaaactaatctttgggcaagggacaactttacaagtaaaaccagatatccagaac SEQ ID NO: 1509 TRAJ38*01 aaagctttctatgactgtgtaatgctggcaacaaccgtaagctgatttggggattgggaacaagcctggcagtaaatccgagtgagtcttcgtgttaact SEQ ID NO: 1510 TRAJ39*01 cagccgaagatcactgtgtgaataataatgcaggcaacatgctcacctttggagggggaacaaggttaatggtcaaaccccgtgagtatctctgctgaat SEQ ID NO: 1511 TRAJ4*01 aagcaccatctgattgtgtgttttctggtggctacaataagctgatttttggagcagggaccaggctggctgtacacccatgtgagtatgaccctgcaag SEQ ID NO: 1512 TRAJ40*01 tatgttggtttatgtagagacacataacactgtgactacctcaggaacctacaaatacatctttggaacaggcaccaggctgaaggttttagcaagt SEQ ID NO: 1513 TRAJ41*01 ttagggagaacgcactgtggaactcaaattccgggtatgcactcaacttcggcaaaggcacctcgctgttggtcacaccccgtgagtttttgtggtttac SEQ ID NO: 1514 TRAJ42*01 agccccataggactgtgtgaattatggaggaagccaaggaaatctcatctttggaaaaaggcactaaactctctgttaaaccaagtaagtgttggggattc SEQ ID NO: 1515 TRAJ43*01 ttgttagagcatgtattactgtgacaataacaatgacatgcgctttggagcagggaccagactgacagtaaaaccaagtaagttgggggaatgggtcaat SEQ ID NO: 1516 TRAJ44*01 aggtttctgttatgaagcatctcacagtgtaaataccggcactgccagtaaactcacctttgggactggaacaagacttcaggtcacgctcggt SEQ ID NO: 1517 TRAJ45*01 agggttggcccagagtgtgtattcaggaggaggtgctgacggactcacctttggcaaagggactcatccaatcatccagccctgtaagtgctttgcctg SEQ ID NO: 1518 TRAJ46*01 aagctgctgacagccgtgagaagaaaagcagcggagacaagctgacttttgggaccgggactcgtttagcagttaggcccagtaagtctgagcagaaagt SEQ ID NO: 1519 TRAJ47*01 gtagaggagtttgacgctgtgtggaatatggaaacaaattggtctttggcgcaggaaccattctgagagtcaagtcctgtgagtataaaacacactcaag SEQ ID NO: 1520 TRAJ47*01 gtgtactattgcatctcggccctggaatatggaaacaagctggtctttggcgcaggaaccattctgagagtcaagtcctatatccagaaccctgaccctg SEQ ID NO: 1521 TRAJ48*01 atgacttagaacactgtgtatctaactttggaaatgagaaattaacctttgggactggaacaagacftcaccatcatacccagtaagttcttcatccttgg SEQ ID NO: 1522 TRAJ48*01 tgttgagcttcctatcacagtggaacaccggtaaccagttctattttgggacagggacaagtttgacggtcattccaagtaagtcaaagaaaattttcca SEQ ID NO: 1523 TRAJ5*01 tactgtgatgtaccagggtgtggacacgggcaggagagcatttacttttgggagtggaacaagactccaagtgcaaccaagtaagtacccaaacttaggc SEQ ID NO: 1524 TRAJ50*01 taaaggtttggatggctgtgtgaaaacctcctacgacaaggtgatatttgggccagggacaagcttatcagtcattccaagtaagtgtccctggggtgct SEQ ID NO: 1525 TRAJ51*01 aaactccctgaagcagggagatgcgtgacagctatgagaagctgatatttggaaaggagacatgactaactgtgaagccaagcaagctggaaagacctaa SEQ ID NO: 1526 TRAJ52*01 gcctccagtgcagtgctaatgctggtggtactagctatggaaagctgacatttggacaagggaccatcttgactgtccatccaagtaagtgtaacaagac SEQ ID NO: 1527 TRAJ53*01 agccttctgtggctgtgagaatagtggaggtagcaactataaactgacatttggaaaaggaactctcttaaccgtgaatccaagtaagtttgaagggagt SEQ ID NO: 1528 TRAJ54*01 taaagcctcgtgctgtggtgtaattcagggagcccagaagctggtatttggccaaggaaccaggctgactatcaacccaagtaagtatgacagggtgaag SEQ ID NO: 1529 TRAJ55*01 gaggatggatccctgttagtgacaagtgctggtaatgctcctgttggggaaaggggatgagtacaaaaataaatccaagtaagtgtggagggacaagaag SEQ ID NO: 1530 TRAJ56*01 agatcctcgtgtcattgtgttatactggagccaatagtaagctgacatttggaaaaggaataactctgagtgttagaccaggtatgttttaatgaatgtt SEQ ID NO: 1531 TRAJ57*01 aagcagtctgtgggggtgtaactcagggcggatctgaaaagctggtctttggaaagggaacgaaactgacagtaaacccatgtaagtctgaataatgctt SEQ ID NO: 1532 TRAJ58*01 aagcccctcagcacagtgtttaagaaaccagtggctctaggttgacctttggggaaggaacacagctcacagtgaatcctggtaagtggaggggagcatt SEQ ID NO: 1533 TRAJ59*01 atgtaaaggcagcagctcctgtgggaaggaaggaaacaggaaatttacatttggaatggggacgcaagtgagagtgaagctatctttaaaccaaaggtgt SEQ ID NO: 1534 TRAJ6*01 caggttttatcaaaggctgtcctcactgtgtgcatcaggaggaagctacatacctacatttggaagaggaaccagccttattgttcatccgtgtaagt SEQ ID NO: 1535 TRAJ60*01 gtaaagggcctgggcactatgtgaagatcacctagatgctcaactttgggaaggggactgagttaattgtgagcctgggtgagtacctcaactccagagg SEQ ID NO: 1536 TRAJ61*01 taaaggtgcccactcctgtgggtaccgggttaataggaaactgacatttggagccaacactagaggaatcatgaaactcagcaagtaatatttggcagaa SEQ ID NO: 1537 TRAJ7*01 tgtaatacacttacacagtgtgactatgggaacaacagactcgcttttgggaaggggaaccaagtggtggtcataccaagtaagtgagctgggatcctcc SEQ ID NO: 1538 TRAJ8*01 tacagagttatgtcagagtgtgaacacaggctttcagaaacttgtatttggaactggcacccgacttctggtcagtccaagtaagtcaaatctgcagaaa SEQ ID NO: 1539 TRAJ9*01 cgcagtgcaaatcactgtgggaaatactggaggcttcaaaactatctttggagcaggaacaagactatttgttaaagcaagtaagttccatgaaataacc SEQ ID NO: 1540 TRBJ1-1*01 ttttcaccttgacccctgtcactgtgtgaacactgaagctttctttggacaaggcaccagactcacagttgtaggtaagacatttttcaggttcttttgc SEQ ID NO: 1541 TRBJ1-2*01 ttttagagtggctatattcttatgtgctaactatggctacaccttcggttcggggaccaggttaaccgttgtaggtaaggctgggggtctctaggagggg SEQ ID NO: 1542 TRBJ1-3*01 tttgaagtggccctgggaggctgtgctctggaaacaccatatattttggagagggaagttggctcactgttgtaggtgagtaagtcaaggctggacagct SEQ ID NO: 1543 TRBJ1-4*01 ttccttccagtctttaatgttgtgcaactaatgaaaaactgttttttggcagtggaacccagctctctgtcttgggtatgtaaaagacttctttcgggat SEQ ID NO: 1544 TRBJ1-5*01 tttgccacactcatgatgcactgtgtagcaatcagccccagcattttggtgatgggactcgactctccatcctaggtaagttggcagaatcagggtggta SEQ ID NO: 1545 TRBJ1-6*01 ttatctaagcctctgcagctgtgctcctataattcacccctccactttgggaatgggaccaggctcactgtgacaggtatgggggctccactcttgactc SEQ ID NO: 1546 TRBJ1-6*02 ttatctaagcctctgcagctgtgctcctataattcacccctccactttgggaacgggaccaggctcactgtgacaggtatgggggctccactcttgactc SEQ ID NO: 1547 TRBJ2-1*01 ttctgggcagccccttcccactgtgctcctacaatgagcagttcttcgggccagggacacggctcaccgtgctaggtaagaagggggctccaggtgggag SEQ ID NO: 1548 TRBJ2-2*01 tgcgccagggtccccagggctgtgcgaacaccggggagctgttttttggagaaggctctaggctgaccgtactgggtaaggaggcggctggggctccgga SEQ ID NO: 1549 TRBJ2-2P*01 agctgccccactctgagaggggctgtgctgagaggcgctgctgggcgtctgggcggaggactcctggttctgggtgctgggagagcgatggggctctcag SEQ ID NO: 1550 TRBJ2-3*01 ttttgtcctgggcctccaggctgtgagcacagatacgcagtattttggcccaggcacccggctgacagtgctcggtaagcgggggctcccgctgagccc SEQ ID NO: 1551 TRBJ2-4*01 ttctgtgccgcgtctcggggctgtgagccaaaaacattcagtacttcggcgccgggacccggctctcagtgctgggtaagctggggccgccgggggaccg SEQ ID NO: 1552 TRBJ2-5*01 tttttgtgcggggctcgggggccgtgaccaagagacccagtacttcgggccaggcacgcggctcctggtgctcggtgagcgcgggctgctggggcgcggg SEQ ID NO: 1553 TRBJ2-6*01 ttgcggggagtccccgggctgtgctctggggccaacgtcctgactttcggggccggcagcaggctgaccgtgctgggtgagttttcgcgggaccacccgg SEQ ID NO: 1554 TRBJ2-7*01 tttgcatgcgggggtgcacctccgtgctcctacgagcagtacttcgggccgggcaccaggctcacggtcacaggtgagattcgggcgtctccccaccttc SEQ ID NO: 1555 TRBJ2-7*02 tttgcatgcggggatgcacctccgtgctcctacgagcagtacgtcgggccgggcaccaggctcacggtcacaggtgagattcgggcgtctccccaccttc SEQ ID NO: 1556 TRDJ1*01 ttttggaacgtcctcaagtgctgtgacaccgataaactcatctttggaaaaggaacccgtgtgactgtggaaccaagtaagtaactcattatttatctga SEQ ID NO: 1557 TRDJ2*01 tttttcgtaatgacgcctgtggtagtgctttgatagcacaactcttctttggaaagggaacacaactcatcgtggaaccaggtaagttatgcattttact SEQ ID NO: 1558 TRDJ3*01 tgaggcactgtcataatgtgctcctgggacacccgacagatgtttttcggaactggcatcaaactcttcgtggagcccgtgagttgatctttttcctat SEQ ID NO: 1559 TRDJ4*01 atgagacatacaaaaaggtaatgccgccccagacccctgatctttggcaaaggaacctatctggaggtacaacaac SEQ ID NO: 1560 TRGJ1*01 tttttgatatggactgaatcactgtggaattattataagaaactctttggcagtggaacaacactggttgtcacaggtaagtatcggaagaatacaacatt SEQ ID NO: 1561 TRGJ1*02 tactgtgccttgtgggaggtgcttattataagaaactctttggcagtggaacaacacttgttgtcacaggt SEQ ID NO: 1562 TRGJ2*01 ttttgatatggactgaatcactgtggaattattataagaaactctttggcagtggaacaacacttgttgtcacaggtaagtatcggaagaatacaacatt SEQ ID NO: 1563 TRGJP*01 ataaaggcttctcaggtggtgggcaagagttgggcaaaaaaatcaaggtatttggtcccggaacaaagcttatcattacaggtaagttttctttaaattt SEQ ID NO: 1564 TRGJP1*01 gatttttctagaagcttagaccggtgtgataccactggttggttcaagatatttgctgaagggactaagctcatagtaacttcacctggtaagt SEQ ID NO: 1565 TRGJP2*01 gatttttgtagaagcttagaccagtgtgatagtagtgattggatcaagacgtttgcaaaagggactaggctcatagtaacttcgcctggtaagt

TABLE 2.3 Dilution Series Design Total Desired cell Number Equivalent Theoretical desired fraction of of polyclonal final number Jurkat- desired Required Equivalent (A037) DNA dilution DNA of cells configuration Jurkat polyclonal Jurkat DNA required required Water concentration Dilution in 50 μL lymphocytes cells cells (μL) 

(μL) (μL) (ng/μL) 1 2.00E+05 1 2.00E+05 0 13.21 0.00 36.79 2.80 2 2.00E+05 0.1 2.00E+04 1.80E+05 13.21 of 1 in 10 2.79 34.00 2.80 dilution of Dilution 1 3 2.00E+05 0.01 2.00E+03 1.98E+05 13.21 of 1 in 10 3.07 33.72 2.80 dilution of Dilution 2 4 2.00E+05 0.001 2.00E+02 2.00E+05 13.21 of 1 in 10 3.09 33.70 2.80 dilution of Dilution 3 5 2.00E+05 0.0001 2.00E+01 2.00E+05 13.21 of 1 in 10 3.10 33.69 2.80 dilution of Dilution 4 6 2.00E+05 0.00001 2.00E+00 2.00E+05 13.21 of 1 in 10 3.10 33.69 2.80 dilutiono f Dilution 5  

 Assumptions of note: Stock Jurkat Cell Line DNA Concentration: 10.6 ng/μL; Presumes lymphocyte DNA content: 0.0007 ng/cell

indicates data missing or illegible when filed

TABLE 2.4 Clinical, Pathology & Outcome Data Parameters Clinical Data Treatment Data Outcome Data Parameters Pathology Data Parameters Parameters Parameters Age at Diagnosis Morphology (small cell, large cell First-line therapy Birthdate anaplastic) Gender Background (mixed or uniform Transplant (Yes/No) Diagnosis Date inflammatory infiltrates) Primary Site of Bone Marrow Status of Diagnosis Second-line or Date of Last Follow- involvement (% of involvement by tumor, if subsequent additional up applicable) therapies Performance Primary Specimen Disposition Status immunohistochemistry (0 = Alive; (positive/negative) 1 = Deceased) B symptoms CD2 International CD3 Prognostic Index Stage CD4 CBC at diagnosis CD5 Hb CD7 MCV CD8 Plt CD10 Neut CD21 Mono CD23 Eo CD30 Lymph CD56 Other CD57 Chemistry BCL6 LDH KI67 Uric Acid EBER Albumin ALK Alk-Phos PD1 ALT CXCL-13 AST Primary Speciment Flow Cytometry (positive/negative) BUN CD45 Calciura CD2 Chloride CD3 CO2 CD5 Creatinine CD4 Glucose CD7 Potassium CD8 Sodium CD10 Total Bilirubin CD19 Total protein CD20 CD30 TCR alpha/beta TCR gamma/delta Molecular Clonality (clonal/polyclonal) Other Cytogenetics (normal/abnormal) Classical FISH Serology (positive/negative) HIV HTLV-1

TABLE 2.5 Sample descriptions and flow cytometry data of the 6 actual patient lymphocyte specimens used for analytical validation Flow-cytometry Number of Cells Features (if Input for DNA “Clonal/Oligoclonal” vs Sample Name Description available) Isolation “Polyclonal” A037 Healthy Donor N/A 10,000,000 Polyclonal Patient Peripheral Blood Mononuclear Cells OV7 Mixed Ovarian 90% CD3+ 10,000,000 Polyclonal Tumour- 10% CD4+ Infiltrating 70% CD8+ Lymphocytes expanded with IL- 2 treatment EZM Cell suspension of N/A 10,000,000 Uncertain melanoma tumour (possible admixed with brisk CD3 tumour cells) infiltration TIL2 Melanoma 97% CD8+ 10,000,000 Oligoclonal tumour-infiltrating lymphocytes expanded in IL-2 STIM1 MART1-specific 99% CD8+ 10,000,000 Clonal/Oligoclonal cell line made from peptide stimulation of healthy donor PBMCs, FACS sorting and expansion of tetramer+ cells L2D8 gp100-specific ~100% CD8+ 10,000,000 Clonal/Oligoclonal tumour-infiltrating lymphocyte clone

TABLE 2.6 Cell lines used for analytical validation Reference Previously Documented/ Cell Line Collection # Known TRGR Configurations CEM (CCRF- ATCC CCL-119 TRBV3-1*01-TRBD1*01- CEM) TRBJ2-3*01 TRBJ1-5-TRBJ2-1 (partial rearrangement) TRBV9-TRBD2 (partial rearrangement) TRGV3-TRGJ1/TRGJ2 TRGV4-TRGJ1/TRGJ2 Jurkat DSMZ ACC-282 TRAV8-4-TRAJ3 TRBV12-3-TRBJ1-2 (partial rearrangement) MOLT4 ATCC CRL- TRBV20-1*01-TRBD2*01- 1582 TRBJ2-1*01 TRBV10-3-TRBD1*01-TRBJ2-5 TRGV2-TRGJP1 TRGV2-TRGJP2 SUPT1 ATCC CRL- TRBV9*01-TRBD2*01-TRBJ2-1*01 1942 TRGV3-TRGJ1/TRGJ2 TRGV4-TRGJ1/TRGJ2

TABLE 1.1 Capture Sample Method Data Sample Sample Protocol Type Library input (ng) A037 healthy reference Sample_A037_PBMC_TCR_A_all A037_PBMC CapSeq_One-Step_V 100 Sample_A037_PBMC_TCR_B_all A037_PBMC CapSeq_One-Step_V 200 Sample_A037_PBMC_TCR_D_all A037_PBMC CapSeq_One-Step_V 600 Sample_A037_PBMC_TCR_E_all A037_PBMC CapSeq_One-Step_V 800 Sample_A037_PBMC_TCR_F_all A037_PBMC CapSeq_One-Step_V 1000 Sample_A037_PBMC_TCR_G_all A037_PBMC CapSeq_One-Step_V 200 Sample_A037_PBMC_TCR_H_all A037_PBMC CapSeq_One-Step_V 600 Sample_A037_PBMC_TCR_J_all A037_PBMC CapSeq_One-Step_V 200 Sample_A037_PBMC_TCR_K_all A037_PBMC CapSeq_One-Step_V 600 Sample_A037_PBMC_TCR_L_all A037_PBMC CapSeq_One-Step_V 1000 Sample_16_01_A037_PBMC_TCR_F_all A037_PBMC CapSeq_One-Step_V 500 Sample_16_01_A037_PBMC_TCR_H_all A037_PBMC CapSeq_One-Step_V 250 Sample_A037_S1_all A037_PBMC CapSeq_One-Step_VI 100 Sample_A037_PBMC_1S_all A037_PBMC CapSeq_One-Step_VI 100 Sample_16_11_A037_PBMC_TCR_VI_all A037_PBMC CapSeq_One-Step_VI 100 Sample_A037_CD3_1S_all A037_CD3 CapSeq_One-Step_VI 100 Cell lines and flow sorted M36_EZM flow_sorted CapSeq_One-Step_VI 100 M36_TIL2 flow_sorted CapSeq_One-Step_VI 100 DV7-TIL2 flow_sorted CapSeq_One-Step_VI 100 SE14-2005 cell_line CapSeq_One-Step_VI 100 SE14-2033 cell_line CapSeq_One-Step_VI 100 SE14-2034 cell_line CapSeq_One-Step_VI 100 SE14-2035 cell_line CapSeq_One-Step_VI 100 STIM1 flow_sorted CapSeq_One-Step_VI 100 L2D8 flow_sorted CapSeq_One-Step_VI 100 Patient samples M14-10124 patient_tumor CapSeq_One-Step_VI 100 M14-11153 patient_tumor CapSeq_One-Step_VI 100 M14-11567 patient_tumor CapSeq_One-Step_VI 100 M14-11587 patient_tumor CapSeq_One-Step_VI 100 M14-11721 patient_tumor CapSeq_One-Step_VI 100 M14-11770 patient_tumor CapSeq_One-Step_VI 100 M14-12217 patient_tumor CapSeq_One-Step_VI 100 M14-12649 patient_tumor CapSeq_One-Step_VI 100 M14-12728 patient_tumor CapSeq_One-Step_VI 100 M14-12753 patient_tumor CapSeq_One-Step_VI 100 M14-13167 patient_tumor CapSeq_One-Step_VI 100 M14-13300 patient_tumor CapSeq_One-Step_VI 100 M14-13750 patient_tumor CapSeq_One-Step_VI 100 M14-14570 patient_tumor CapSeq_One-Step_VI 100 M14-14625 patient_tumor CapSeq_One-Step_VI 100 M14-14907 patient_tumor CapSeq_One-Step_VI 100 M14-14951 patient_tumor CapSeq_One-Step_VI 100 M14-14962 patient_tumor CapSeq_One-Step_VI 100 M14-1508 patient_tumor CapSeq_One-Step_VI 100 M14-15119 patient_tumor CapSeq_One-Step_VI 100 M14-3271 patient_tumor CapSeq_One-Step_VI 100 M14-4454 patient_tumor CapSeq_One-Step_VI 100 M14-5819 patient_tumor CapSeq_One-Step_VI 100 M14-5875 patient_tumor CapSeq_One-Step_VI 100 M14-6143 patient_tumor CapSeq_One-Step_VI 100 M14-6430 patient_tumor CapSeq_One-Step_VI 100 M14-6443 patient_tumor CapSeq_One-Step_VI 100 M14-6502 patient_tumor CapSeq_One-Step_VI 100 M14-6885 patient_tumor CapSeq_One-Step_VI 100 M14-7046 patient_tumor CapSeq_One-Step_VI 100 M14-7049 patient_tumor CapSeq_One-Step_VI 100 M14-7053 patient_tumor CapSeq_One-Step_VI 100 M14-7107 patient_tumor CapSeq_One-Step_VI 100 M14-7554 patient_tumor CapSeq_One-Step_VI 100 M14-7568 patient_tumor CapSeq_One-Step_VI 100 M14-7691 patient_tumor CapSeq_One-Step_VI 100 M14-7700 patient_tumor CapSeq_One-Step_VI 100 M14-7782 patient_tumor CapSeq_One-Step_VI 100 M14-7862 patient_tumor CapSeq_One-Step_VI 100 M14-7884 patient_tumor CapSeq_One-Step_VI 100 M14-7992 patient_tumor CapSeq_One-Step_VI 100 M14-8132 patient_tumor CapSeq_One-Step_VI 100 M14-8272 patient_tumor CapSeq_One-Step_VI 100 M14-8639 patient_tumor CapSeq_One-Step_VI 100 M14-8668 patient_tumor CapSeq_One-Step_VI 100 M14-8740 patient_tumor CapSeq_One-Step_VI 100 M14-8913 patient_tumor CapSeq_One-Step_VI 100 M14-8914 patient_tumor CapSeq_One-Step_VI 100 M14-9212 patient_tumor CapSeq_One-Step_VI 100 M14-9801 patient_tumor CapSeq_One-Step_VI 100 M15-1195 patient_tumor CapSeq_One-Step_VI 100 M15-1330 patient_tumor CapSeq_One-Step_VI 100 M15-1470 patient_tumor CapSeq_One-Step_VI 100 M15-1556 patient_tumor CapSeq_One-Step_VI 100 M15-1825 patient_tumor CapSeq_One-Step_VI 100 M15-1867 patient_tumor CapSeq_One-Step_VI 100 M15-1883 patient_tumor CapSeq_One-Step_VI 100 M15-237 patient_tumor CapSeq_One-Step_VI 100 M15-2603 patient_tumor CapSeq_One-Step_VI 100 M15-2779 patient_tumor CapSeq_One-Step_VI 100 M15-3091 patient_tumor CapSeq_One-Step_VI 100 M15-587 patient_tumor CapSeq_One-Step_VI 100 M15-795 patient_tumor CapSeq_One-Step_VI 100 M15-933 patient_tumor CapSeq_One-Step_VI 100

TABLE 1.2 Capture Sample Read Counts Sample

Patient samples

indicates data missing or illegible when filed

TABLE 1.3 Capture Sample V and J Calls Sample

Patient samples

indicates data missing or illegible when filed

TABLE 1.4 Capture Sample Unique V and J Calls Sample

Patient samples

indicates data missing or illegible when filed

TABLE 1.5 Capture Sample Unique CDR3 Calls Sample

Patient samples

indicates data missing or illegible when filed

TABLE 2 Cell Line Identified VJ Rearrangements Cell Reference Alpha Beta Gamma Delta Line Internal Collection # Previously Documented/Known TCR Configurations CEM SE14- ATCC CCI NA TRGV3 TRG1/TRG2 NA 2035 119 TRBJ1-5-TRBJ2-1 TRGV4 TRG1/TRG2 (partial rearrangement) TRBV9-TRBO2 (partial rearrangement) Observed Alpha (Counts) Beta (Counts) Gamma (Counts) Delta TRAV27#1TRU40#1 TRBV3 1#1TRB7 3#1

NO (987) (1087) TRAV29_OVS#1TRAJ4#1 TRAV3-2#3TRBJ2-3#1 TRGV3#2TRGJ2#1 (765) (512) (604) TRAV29_DVS#3TRAJ4#1 TRAV3-2#3TRBJ2-4#1 TRGV3#1TRGJ2#1 (45) (45) (228) TRAV27#3TRAJ40#1 TRBV3-1#1TRBJ2-5#J TRGVS#2TRGJ2#1 (3) (8) (106) TRAV27#2TRAJ40#1 TRBV3-1#1TRBJ2-4#1 TRGV4#1TRGJ2# (1) (4) TRAV8-G#2TRAJ20#1 TR8V3-1#1TRBJ2-6#1 (2) (2) TRBV3-2#3TRBJ2-6#1 (2) TRBV9#2TRBJ2-1#1 (2) Previously Documented/Known TCR Configurations SE14- DSMZACC- TRBV12-3 TRBJ2-2 Jurkat 2033 282 TRAV8-4 TRAJ3 (partial rearrangement) TRGV8-TRG2 NA TRGV-1 TRGJ Observed TRAV8-4#6TRAJ3#1 TRBV12-4#1TRBJ3-2#1 TRGVB#1TRGJ2#3 NO (1000) (608) TRAV8-4#2TRAJ3#2 TRBV12-4#2TRBJ2-2#1

(118) (137) TRAV12-3#2TRAJ26#1 TRBV12-3#1TRB8J1-2#1

(16) (16) TRAV17#1TRAJ24#2

(7) TRAV17#1TRAJ16#1

(4) TRAV17#1TRAJ29#1 (3) TRAV14_DV4#2TRAJ224#2 (2) TRAV26#2TRAJ29#1 (1) TRAV17#1TRAJ32#1 (1) TRAV29_DV5#1TRAJ4#1 (1) TRAV9-2#1TRAJ29#1 (1) SE14- ATCC CRB- Previously Documented/Known TCR Configurations MCLT4 2034 1582 NA TRBV20-1

TRGV2-TRGIP1 NA

TRGV2 TRGIP2 Observed TRAV1-1#1TRAJ33#1 TRBY20

TRGV2#1 TRGJP2#1 NO (799) (937) (524) TRAV1-1#1TRAJ23#2

TRGV2#2TRGIP1#1 (621) (724) (496) TRAV1-1#2TRAJ24#2 TRBV20_DR9-283TR8J2-1#1 TRGV8#2TRGIP1#1 (79) (384) (1) TRAV1-1#2TRAJ33#1 TRBV10-3#2TRBJ2-6#1 (1) (91) TR5V20-1#7TRBJ2-1#1 (8) TR8V20_OR9-2#8THBJ2-2#2 (2) TR8V20-1#1TRBJ2-2#1 (1) TRBV20-1#3TR8J2-1#1 (1) SE14- ATCC CRL- Previously Documented/Known TCR Configurations SUPT2 2005 1942 NA

TRGV3 TRGJ1/TRGBJ2 NA

Observed TRAV1-1#3TRAJ12#1

NO (1120) (971) (683) TRAV2-1#2TRAJ8#1

(836) (137) TRAV2-1#2TRAJ8#1 TRBV9#2TRBJ2-2#2

(263) (9) TRAV2-1#2TRAJ8#1 TRBV9#2TRBJ2-2#2

(263) (9) TRAV2-1#2TRAJ8#1 TRBV9#2TRBJ2-2#2 TRBV9#2TRBJ2-2#2 (263) (9) (9) TRAV2-1#2TRAJ8#1 TRBV9#2TRBJ2-2#2 (263) (9) TRBV9#2TRBJ2-2#2 (9) TRBV9#2TRBJ2-2#2 (9) TRBV9#2TRBJ2-2#2 (9) TRBV9#2TRBJ2-2#2 (9) http://www.imgt.org/IMGTrepertoire/Probes/Rearrangements%20and%20junctions/human/Hu_TRrea.html}

indicates data missing or illegible when filed

TABLE 3 Sanger Sequencing Results Composition

TRAV1

877 TRAV1 877 TRAV1 877 TRAV1 877 TRAV17 & 877 TRAV27 877 TRAV 877 TRAV 877

877 TRAV 877 TRAV 877 TRAV 877 TRAV 877 TRAV 877

877 TRB 877 TRB 877 TRB 877 TRB 877 TRB 877 TRB 877 TRB 877

877 TRB 877 TRB 877 TRB 877

indicates data missing or illegible when filed

TABLE 4 SEQ ID NO Name Sequence SEQ ID NO: 1566 TRAV102*02-RIGHT caggtcgtttttcttcattccttagtcgctctgatagttatggttacctccttctacaggagctccagatgaaagactctgcctcttacttctgcgct gt SEQ ID NO: 1567 TRAV1-2*02-RIGHT catctgggttcaacgggctgttctggtaccagcaacatgctggcgaagcacccacatttctgtcttacaatgttctggatggtctggaggagaa aggtcg SEQ ID NO: 1568 TRAV12-1*02-RIGHT acagcacacgtcaatagagccagccagtatatttccctgctcatcagagactccaagctcagtgattcagccacctacctctgtgtggtgaaca ttcgcc SEQ ID NO: 1569 TRAV12-2*02-RIGHT gtttacagcacagctcaataaagccagccagtatgtttctctgctcatcagagactcccagcccagtgattcagccacctacctctgtgccgtgt accac SEQ ID NO: 1570 TRAV12-2*03-RIGHT aaggtttacagcacagctcaataaagccagccagtatgtttctctgctcatcagagactcccagcccagtgattcagccacctacctctgtgcc gtgaac SEQ ID NO: 1571 TRAV12-3*02-RIGHT aggtttacagcacaggtcgataaatccagcaagtatatctccttgttcatcagagactcacagcccagtgattcagccacctacctctgtgcaat gagcg SEQ ID NO: 1572 TRAV13-1*02-RIGHT tgttacattgaacaagacagccaaacatttctccctgcacatcacagagacccaacctgaagactcggctgtctacttctgtgcagcaagtagg aaggac SEQ ID NO: 1573 TRAV1301*03-RIGHT gcttattatagacattcgttcaaatgtgggcgaaaagaaagaccaacgaattgctgttacattgaacaagacagccaaacatttctcccctgcag atcaca SEQ ID NO: 1574 TRAV13-2*02-RIGHT caaagagtcaccgtttattgaataagacagtgaaacatctctctctgcaaattgcagctactcaacctggagactcagctgtctacttttgtgc agaga SEQ ID NO: 1575 TRAV14/DV4*03-RIGHT aggtcgctactcattgaatttccagaaggcaagaaaatccgccaaccttgtcatctccgcttcacaactgggggactcagcaatgtatttctgtg caatg SEQ ID NO: 1576 TRAV14/DR4*04-RIGHT gcaacagaaggtcgctactcfattgaattccagaaggcaagaaaatccgccaaccttgtcatctccgcttcacaactgggggactcagcaatg tacttct SEQ ID NO: 1577 TRAV2*02-RIGHT gggacgatacaacatgacctatgaacggttctcttcatcgctgctcatcctccaggtgcgggaggcagatgctgctgtttactactgtgctgtgg cctgg SEQ ID NO: 1578 TRAV20*02-RIGHT aaaggagaaagaaaggctaaaagccacattaacaaagaaggaaagctttctgcacatcacagcccctaaacctgaagactcagccacttat ctctgtgct SEQ ID NO: 1579 TRAV20*03-RIGHT agaaaaggagaagaaggctaaaagccacattaacaaagaaggaaagctttctgcacatcacagcccctaaacctgaagactcagccac ttatctctgt SEQ ID NO: 1580 TRAV20*04-RIGHT aaaggagaaagaaaggctaaaagccacattaacaaagaaggaaagctttctgcacatcacagcccctaaacctgaagactcagccacttat ctctgtgct SEQ ID NO: 1581 TRAV21*02-RIGHT aagtggaagacttaatgcctcgctggataaatcatcaggacgtagtactttatacattgcagcttctcagcctggtgactcagccacctacctct gtgct SEQ ID NO: 1582 TRAV23/DV6*02-RIGHT agattcacaatctccttcaataaaagtgccaagcagttctcattgcatatcatggattcccagcctggagactcagccacctacttctgtgcagc aagcg SEQ ID NO: 1583 TRAV23/DV6*03-RIGHT agattcacaatctccttcaataaaagtgccaagcagttctcattgcatatcatggattcccagcctggagactcagccacctacttctgtgcagc aagca SEQ ID NO: 1584 TRAV23/DV6*04-RIGHT gaaagaaggaagattcacaatctccttcaataaaagtgccaagcagttctcattgcatatcatggattcccagcctggagactcagccaccta cttctgt SEQ ID NO: 1585 TRAV24*02-RIGHT ggacgaataagtgccactcttaataccaaggagggttacagctatttgtacatcaaaggatcccagcctgaagattcagccacatacctcgtg ccttta SEQ ID NO: 1586 TRAV26-1*02-RIGHT ctctgatcatcacagaagacagaaagtccagcaccttgatcctgccccacgctacgctgagagacactgctgtgtactattgcatcgtcagaga ttgggt SEQ ID NO: 1587 TRAV26-1*03-RIGHT caatgaaatggcctctctgatcatcacagaagacagaaagtccagcaccttgatcctgccccacgctacgctgagagacactgctgtgtactat tgcatc SEQ ID NO: 1588 TRAV26-2*02-RIGHT ccctcccagggtccagagtacgtgattcatggtcttacaagcaatgtgaacaacagaatggcctgtgtggcaatcgctgaagacagaaagtcc agtacct SEQ ID NO: 1589 TRAV27*02-RIGHT tgaagagactaacctttcagtttggtgatgcaagaaaggacagttctctccacatcactgcggcccagcctggtgatacaggccactacctcg tgcagg SEQ ID NO: 1590 TRAV27*03-RIGHT gctgaagagactaacctttcagtttggtgatgcaagaaaggacagttctctccacatcactgcagcccagactggtgatacaggcctctacctc tgtgca SEQ ID NO: 1591 TRAV29/DV5*02-RIGHT aagattcactgttttcttaaacaaaagtgccaagcacctctctctcgacattgtgccctcccagcctggagactctgcagtgtacttctgtgcagc aagc SEQ ID NO: 1592 TRAV29/DV5*03-RIGHT agattcactgttttcttaaacaaaagtgccaagcacctctctctgcacattgtgccctcccagcctggagactctgcagtgtacttctgtgcagta agcg SEQ ID NO: 1593 TRAV3*02-RIGHT ctttgaagctgaatttaacaagagccaaacctccttccacctgaagaaaccatctgcccttgtgagcgactccgctttgtacttctgtgctgtgag accc SEQ ID NO: 1594 TRAV30*02-RIGHT tcgtgaaaaaatatctgcttcatttaatgaaaaaaagcagcaaagctccctgtaccttacggcctcccagctcagttactcaggaacctacttct gcggg SEQ ID NO: 1595 TRAV30*03-RIGHT tcatgaaaaaatatctgcttcattaatgaaaaaaagcggcaaagctccctgtaccttacggcctcccagctcagttactcaggaacctacttct gcggc SEQ ID NO: 1596 TRAV30*04-RIGHT tcctgatgatattactgaagggtggagaacagaagcgtcatgaaaaaatatctgcttcatttaatgaaaaaaagcagcaaagctccctgtacc ttacggc SEQ ID NO: 1597 TRAV35*02-RIGHT aaatggaagactgactgctcagtttggtataaccagaaaggacagcttcctgaatatctcagcatccatacctagtgatgtaggcatctacttct gtgct SEQ ID NO: 1598 TRAV36/DV7*02-RIGHT ggaagactaagtagcatattagataagaaagaacttttcagcatcctgaacatcacagccacccagaccggagactcggccgtctacctctgt gctgtgg SEQ ID NO: 1599 TRAV36/DV7*03-RIGHT gtcaggaagactaagtagcatattagataagaaagaacttttcagcatcctgaacatcacagccacccagaccggagactcggccgtctacct ctgtgct SEQ ID NO: 1600 TRAV36/DV7*04-RIGHT tcaggaagactaagtagcatattagataagaaagaacttttcagcatcctgaacatcacagccacccagaccggagactcggccgtctacctc tgtgctg SEQ ID NO: 1601 TRAV38-1*02-RIGHT gagaatcgtttctctgtgaacttccagaaagcagccaaatccttcagtctcaagatctcagactcacagctgggggacactgcgatgtatttctg tgctt SEQ ID NO: 1602 TRAV38-1*03-RIGHT aatcgtttctctgtgaacttccagaaagcagccaaatccttcagtctcaagatctcagactcacagctgggggacactgcgatgtatttctgtgc tttca SEQ ID NO: 1603 TRAV38-1*04-RIGHT ggagaatcgtttctctgtgaacttccagaaagcagccaaatccttcagtctcaagatctcagactcacagctgggggacactgcgatgtatttct gtgca SEQ ID NO: 1604 TRAV6*02-RIGHT gaaagaaagactgaaggtcacctttgataccacccttaaacagagtttgtttcatatcacagcctcccagcctgcagactcagctacctacctct gtgct SEQ ID NO: 1605 TRAV6*03-RIGHT gaaagaaagactgaaggtcacctttgataccacccttaaacagagtttgtttcatatcacagcctcccagcctgcagactcagctacctacctct gtgct SEQ ID NO: 1606 TRAV6*04-RIGHT gaaagaaagactgaaggtcacctttgataccacccttaaacagaagtttgtttcatgtcacagcctcccagcctgcagacttagctacctacctct gtgct SEQ ID NO: 1607 TRAV6*05-RIGHT gaaagaaagactgaaggtcacctttgataccacccttaaacagagtttgtttcatatcacagcctcccagcctgcagactcagctacctacctct gtgct SEQ ID NO: 1608 TRAV6*06-RIGHT ccaggaagaggccctgttttcttgctactcatacgtgaaaatgagaaagaaaaaaggaaagaaagactgaaggtcacctttgataccaccctt aaccaga SEQ ID NO: 1609 TRAV8-1*02-RIGHT ttttcaggggaatccactggttaaaggcatcaagggcgttgaggctgaatttataaagagtaaattctcctttaatctgaggaaaccctctgtgca gtgga SEQ ID NO: 1610 TRAV8-2*02-RIGHT tttaagaagagtgaaacctccttccacctgacgaaaccctcagcccatatgagcgacgcggctgagtacttctgtgttgtgacccgtcacgagc tttcag SEQ ID NO: 1611 TRAV8-3*02-RIGHT aggctttgaggctgaatttaagaggagtcaatcttccttcaacctgaggaaaccctctgtgcattggagtgatgctgctgagtacttctgtgctgt ggtt SEQ ID NO: 1612 TRAV8-3*03-RIGHT tattaaaggctttgaggctgaatttaagaggagtcaatcttccttcaatctgaggaaaccctctgtgcattggagtgatgcgtctgagtacttctg tgct SEQ ID NO: 1613 TRAV8-4*02-RIGHT gaatttaagaagagtgaaacctccttccacctgacaaaaccctcagcccatatgagcgacgcggctgagtacttctgtgctgtgagtgatctcg aaccga SEQ ID NO: 1614 TRAV8-4*03-RIGHT catcaacggttttgaggctgaatttaagaagagtgaaacctccttccacctgacgaaaccctcagcccatatgagcgacgcggctgagtacttc tgtgct SEQ ID NO: 1615 TRAV8-4*04-RIGHT aggcatcaacggttttgaggctgaatttaagaagagtgaaacctccttccacctgacgaaaccctcagcccatatgagcgacgcggctgagta cttctgt SEQ ID NO: 1616 TRAV8-4*05-RIGHT ggctgaatttaagaagagtgaaacctccttccacctgacgaaaccctcagcccatatgagcgacgcggctgagtacttctgtgctgtgagtga gtctcca SEQ ID NO: 1617 TRAV8-4*06-RIGHT gaatttaagaagagtgaaacctccttccacctgacgaaacccgcagcccatatgagcgacgcggctgagtacttctgtgctgtgagtgatctcg aaccga SEQ ID NO: 1618 TRAV8-4*07-RIGHT acggttttgaggctgaatttaaaaagagtgaaacctccttccacctgacgaaaccctcagcccatatgaccgacccggctgagtacttctgtgc tgtgag SEQ ID NO: 1619 TRAV9-2*02-RIGHT caacaaaggttttgaagccacataccgtaaagaaaccacttctttccacttggagaaaggctcagttcaagtgtcagactcagcggtgtacttc tgtgct SEQ ID NO: 1620 TRAV9-2*03-RIGHT caacaaaggttttgaagccacatccgtaaggaaaccacttctttccacttggagaaggctcagttcaagtgtcagactcagcggtgtacttc tgtgct SEQ ID NO: 1621 TRAV9-2*04-RIGHT caacaaaggttttgaagccacataccgtaaggaaaccacttctttccacttggagaasaaggctcagttcaagtgtcagactcagcggtgtacttc tgtgct SEQ ID NO: 1622 TRBV10-1*03-RIGHT ctaacaaaggagaagtctcagatggctacagtgtctctagatcaaacacagaggacctccccctcactctgtagtctgctgcctcctcccagac atctgt SEQ ID NO: 1623 TRBV10-2*02-RIGHT agataaaggagaagtccccgatggctacgttgtctccagatccaagacagagaatttccccctcactctggagtcagctacccgctcccagac atctgtg SEQ ID NO: 1624 TRBV10-3*03-RIGHT agaagtctcagatggctatagtgtctctagatcaaagacagaggatttcctcctcactctggagtccgctaccagctcccagacatctgtgtact tctgt SEQ ID NO: 1625 TRBV10-3*04-RIGHT agaagtctcagatggctatagtgtctctagatcaaagacagaggatttcctcctcactctggagtccgctaccagctcccagacatctgtgtact tctgt SEQ ID NO: 1626 TRBV11-2*02-RIGHT ggatcgattttctgcagagaggctcaaaggagtagactccactctcaagatccagcctgcaaagcttgagaactcggccgtgtatctctgtgcc agcagt SEQ ID NO: 1627 TRBV11-2*03-RIGHT ggatcgattttctgcagagaggctcaaaggagtagactccactctcaagatccaacctgcaaagcttgaggactggccgtgtatctctgtgcc agcagc SEQ ID NO: 1628 TRBV11-3*02-RIGHT ggatcgattttctgcagagaggctcaaaggagtagactccactctcaagatccagtctgcagagcttggggactcggccgtgtatctctgtgcc agcagc SEQ ID NO: 1629 TRBV11-3*03-RIGHT ggatcgattttctgcagagaggctcaaaggagtagactccactctcaagatccagccagtagagcttggggactcggccatgtatctctgtgcc agcagc SEQ ID NO: 1630 TRVV12-4*02-RIGHT tcgattctcagctaagatgcctaatgcatcattctccactctgaggatccagccctcagaacccagggactcagctgtgtacttctgtgccagca gttta SEQ ID NO: 1631 TRBV13*02-RIGHT tgatcgattctcagctcaacagttcagtgactatcattctgaactgaacatgagctccttggagctgggggactcagccctgtacttctgtgcca gcagt SEQ ID NO: 1632 TRBV14*02-RIGHT caatcgattcttagctgaaaggactggagggacgtattctactctgaaggtgcagcctgcagaactggaggattctggagtttatttctgtgcca gcagc SEQ ID NO: 1633 TRBV15*02-RIGHT tgataacttccaatccaggaggccgaacacttctttctgctttcttgacatccgctcaccaggcctgggggacgcagccatgtacctgtgtgcca ccagc SEQ ID NO: 1634 TRBV15*03-RIGHT tgataacttccaatccaggaggccgaacacttctttctgctttctagacatccgctcaccaggcctgggggacgcagccatgtaccagtgtgcc accagc SEQ ID NO: 1635 TRBV16*03-RIGHT ggaaagattttcagctaagtgcctcccaaattcaccctgtagccttgagatccaggctacgaagcttgaggattcagcagtgtatttttgtgcca gcagc SEQ ID NO: 1636 TRBV19*03-RIGHT tgaagggtacagcgtctctcgggagaagaaggaatcctttcctctcactgtgacatcggcccaaaagaacccgacagctttctatctctgtgcc agtagc SEQ ID NO: 1637 TRBV2*02-RIGHT tgatcaattctcagttgaaaggcctgatggatcaaatttcactctgaagatccggtccacaaagctggaggactcagccatgtacttctgtgcca gcagt SEQ ID NO: 1638 TRBV2*03-RIGHT tcaattctcagttgagaggcctgatggatcaaatttcactctgaagatccggtccacaaagctggaggactcagccatgtacttctgtgccagc agtgaa SEQ ID NO: 1639 TRBV20-1*02-RIGHT gaaggacaagtttctcatcaaccatgcaagcctgaccttgtccactctgacagtgaccagtgcccatcctgaagacagcagcttctacatctgc agtgct SEQ ID NO: 1640 TRBV20-1*04-RIGHT ggacaagtttctcatcaaccatgcaagcctgaccttgtccactctgacagtgaccagtgcccatcctgaagacagcagcttctacatctgcagt gctagt SEQ ID NO: 1641 TRBV20-1*05-RIGHT ggacaagtttctcatcaaccatgcaagcctgaccttgtccactctgacagtgaccagtgcccatcctgaagacagcagcttctacatctgcagt gctaga SEQ ID NO: 1642 TRBV20-1*06-RIGHT gaaggacaagtttctcatcaaccatgcaagcctgaccttgtccactctgacagtgaccagtgcccatcctgaagacagcagcttctacatctgc agtgct SEQ ID NO: 1643 TRBV20-1*07-RIGHT ggacaagtttctcatcaaccatgcaagcctgaccttgtccactctgatagtgaccagtgcccatcctgaagacagcagcttctacatctgcagt gctaga SEQ ID NO: 1644 TRBV20/OR9-2*02-RIGHT gaaggacaagtttcccatcaaccatccaaacctgaccttctccgctctgacagtgacctgtgcccatcctgaagacagcagcttctacatctgc agtgct SEQ ID NO: 1645 TRBV23/OR9-2*02-RIGHT gtttttgatttcctttcagaatgaacaagttcttcaagaaatggagatgcacaagaagcgattctcatctcaatgccccaagaacgcaccctgc agcctg SEQ ID NO: 1646 TRBV24/OR9-2*02-RIGHT cagttgatctattgctcctttgatgtcaaaatatataaacaaaagagagatctctgatggatacagtgtctcttgacaggaacaggctaaattct ccctg SEQ ID NO: 1647 TRBV25/OR9-2*02-RIGHT gagttaattccacagagaagggagatctttgctctgagtcaacagtctccagaataaggatagagcgttttcccctgaccctggagtctgccag cccctc SEQ ID NO: 1648 TRBV29-1*02-RIGHT tgacaagtttcccatcagccgcccaaacctaacattctcaagtctgactgtgagcaacatgagccctgaagacagcagcatatatctctgcagc gttgaa SEQ ID NO: 1649 TRBV29-1*03-RIGHT tgacaagtttcccatcagccgcccaaacctaacattctcaactctgactgtgagcaacatgagccctgaagacagcagcatatatctctgcagc gcgggc SEQ ID NO: 1650 TRBV3-1*02-RIGHT tccaaatcgattctcacctaaatctccagacaaagctaaattaaatcttcacatcaattccctggagcttggtgactctgctgtgtatttctgtgcc agc SEQ ID NO: 1651 TRBV3-2*03-RIGHT tcgcttctcacctgactctccagacaaagttcatttaaatcttcacatcaattccctggagcttggtgactctgctgtgtatttctgtgccagcagc caa SEQ ID NO: 1652 TRBV30*02-RIGHT agaatctctcagcctccagaccccaggaccggcagttcatcctgagttctaagaagctcctcctcagtgactctggcttctatctctgtgcctgga gtgt SEQ ID NO: 1653 TRBV30*04-RIGHT ccagaatctctcagcctccagaccccaggaccggcagttcattctgagttctaagaagctcctcctcagtgactctggcttctatctctgtgcctg gagt SEQ ID NO: 1654 TRBV30*05-RIGHT ccagaatctctcagcctccagaccccaggaccggcagttcatcctgagttctaagaagctccttctcagtgactcggcttctatctctgtgcctg ggga SEQ ID NO: 1655 TRBV4-1*02-RIGHT tcgcttctcacctgaatgccccaacagctctctcttaaaccttcacctacacgccctgcagccagaagactcagccctgtatctctgcgccagca gccaa SEQ ID NO: 1656 TRBV4-2*02-RIGHT aagtcgcttctcacctgaatgccccaacagctctcacttatgccttcacctacacaccctgcagccagaagactcggccctgtatctctgtgcca gcacc SEQ ID NO: 1657 TRBV4-3*02-RIGHT aagtcgcttctcacctgaatgccccaacagctctcacttatcccttcacctacacaccctgcagccagaagactcggccctgtatctctgcgcca gcagc SEQ ID NO: 1658 TRBV4-3*03-RIGHT aagtcgcttctcacctgaatgccccaacagctctcacttattccttcacctacacaccctgcagccagaagactcggccctgtatctctgcgcca gcagc SEQ ID NO: 1659 TRBV4-3*04-RIGHT aagtcgcttctcacctgaatgccccaacagctctcacttattcttcacctacacaccctgcagccagaagactcggccctgtatctctgcgcca gcagc SEQ ID NO: 1660 TRBV5-1*02-RIGHT tcgattctcagggcgccagttctctaactctcgctctgagatgaatgtgagcaccttggagctgggggactcggccctttatctttgcgccagcgc ttgc SEQ ID NO: 1661 TRBV5-4*02-RIGHT tcctagattctcaggtctccagttccctaattataactctgagctgaatgtgaacgccttggagctggacgactggccctgtatctctgtgccag cagc SEQ ID NO: 1662 TRBV5-4*03-RIGHT tcctagattctcaggtctccagttccctaattatagctctgagctgaatgtgaacgccttggagctggacgactcggccctgtatctctgtgccag cagc SEQ ID NO: 1663 TRBV5-4*04-RIGHT tcctagattctcaggtctccagttccctaattatagctctgagctgaatgtgaacgccttggagctggacgactcggccctgtatctctgtgccag cagc SEQ ID NO: 1664 TRBV-5*03-RIGHT tgatcgattctcagctcgccagttccctaactatagctctgagctgaatgtgaacgccttgttgctgggggactcggccctgtatctctgtgccag cagc SEQ ID NO: 1665 TRBV-5*03-RIGHT tgatcgattctcagctcgccagttccctaactatagctctgagctgaatgtgaacgccttgttgctgggggactcggccctgtatctctgtgccag cagc SEQ ID NO: 1666 TRBV5-8*02-RIGHT tcctagattttcaggtcgccagttccctaattatagctcgagctgaatgtgaacgccttggagctggaggactcggccctgtatctctgtgccag cagc SEQ ID NO: 1667 TRBV6-2*02-RIGHT tggctacaatgtctccagattaaaaaaacagaatttcctgctggggttggagtcggctgctccctcccaaacatctgtgtacttctgtgccagca gccct SEQ ID NO: 1668 TRBV6-6*03-RIGHT gaatggctacaacgtctccagatcaaccacagaggatttcccgctcaggctggagttggctgctccctcccagacatctgtgtacttctgtgcca gcagt SEQ ID NO: 1669 TRBV6-6*04-RIGHT tggctacaatgtctccagatcaaccacagaggatttcccgctcaggctggagttggctgctccctcccagacatctgtgtacttctgtgccagca gtcga SEQ ID NO: 1670 TRBV6-6*05-RIGHT gaatggctacaacgtctccagatcaaccacagaggatttcccgctcaggctggagttggctgctgcctcccagacatctgtgtacttctgtgcca gcagc SEQ ID NO: 1671 TRBV7-2*03-RIGHT gcttctctgcagagaggactggggaatccgtctccactctgacgatccagcgcacacagcaggaggactcggccgtgtatctctgtaccagca gcttagc SEQ ID NO: 1672 TRBV7-2*04-RIGHT tcgcttctctgcagagaggactgggggatccgtctccactctgacgatccagcgcacacagcaggaggactcggccgtgtatctctgtgccagc agctta SEQ ID NO: 1673 TRBV7-3*04-RIGHT cgatcggttctttgcagtcaggcctgagggatccgtctctactctgaagatccagcgtacagagcggggggactctgccgtgtatctctgtgcca gcagc SEQ ID NO: 1674 TRBV7-3*05-RIGHT cgatcggttctttgcagtcaggcctgagggatccgtctctactccgaagatccagcgcacagagcggggggactcagccgtgtatctctgtgcc agcagt SEQ ID NO: 1675 TRBV7-4*02-RIGHT aacgagacaaatcagggcggcccagtggtcggttctctgcagagaggcctgagagatcgtctccactccgaagatccagcgcacagagcag ggggactca SEQ ID NO: 1676 TRBV7-6*02-RIGHT tgatcggttctctgcagagaggcctgagggatccatctccactctgacgatccagcgcacagagcagcgggactcggccatgtatcgctgtgcc agcagc SEQ ID NO: 1677 TRBV7-7*02-RIGHT tgatcggttctctgcagagagaggcctgagggatccatctccactctgacgattcagcgcacagagcagcgggacttcagccatgtatcgctgtgcc agcagt SEQ ID NO: 1678 TRBV7-8*03-RIGHT tcgcttctttgcagaaaggcctgagggatccgtctccactctgaagatccagcgcacacagcaggaggactccgccgtgtatctctgtgccagc agccga SEQ ID NO: 1679 TRBV7-9*02-RIGHT tcggttctctgcagagaggcctaagggatctttctccaccttggagatccagcgcacagagcagggggactcggccatgtatctctgtgccagc agctta SEQ ID NO: 1680 TRBV7-9*04-RIGHT tcggatctctgcagagaggcctaagggatctttctccaccttggagatccagcgcacagagcagggggactcggccatgtatctctgtgccagc agctct SEQ ID NO: 1681 TRBV7-9*05-RIGHT tcggttctctgcagagaggcctaagggatctctctccaccttggagatccagcgcacagagcagggggactcggccatgtatctctgtgccagc accaaa SEQ ID NO: 1682 TRBV7-9*06-RIGHT tcggttctctgcagagaggcctaagggatctctttccaccttggagatccagcgcacagagcagggggactcggccatgtatctctgtgccagc acgttg SEQ ID NO: 1683 TRBV7-9*07-RIGHT gttctctgcagaggcctaagggatctttctccaccttggagatccagcgcacagaggagggggactcggccatgtatctctgtgccagcagc agcagt SEQ ID NO: 1684 TRBV9*03-RIGHT tgaacgattctccgcacaacagttccctgacttgcactctgaactaaacctgagctctctggagctgggggactcagctttgtatttctgtgccag cagc SEQ ID NO: 1685 TRGV2*02-RIGHT gaagtattatacttacgcaagcacaaggaacaacttgagattgatactgcaaaatctaattgaaaatgactctggggtctattactgtgccacc tgggac SEQ ID NO: 1686 TRBV20-1*03-RIGHT gaaggacaagtttctcatcaaccatgcaagcctgaccttgtccactctgacagtgaccagtgcccatcctgaagacagcagcttctacatctgc agtgct SEQ ID NO: 1687 TRGV6*01-RIGHT gcatgatacttatggaagtagaaggataagctggaaatttatacctccaaaactaaatgaaaatgcctctggggtctattactgtgccacctag gacagg SEQ ID NO: 1688 TRGV4*02-RIGHT gtatgatacttacggaagcacaaggaagaacttgagaatgatactgcgaaatcttattgaaaatgactctggagtctattactgtgccacctgg gatggg SEQ ID NO: 1689 TRGV5P*01-RIGHT gtattatactcatacaccgaggaggtggagctggaatttgagactgcaaaatctaattgaaaatgattctggggtctattactgtgccacctgg ggcagg SEQ ID NO: 1690 TRBV10-3*02-RIGHT gctatagtgtctctagatcaaagacagaggatttcctcctcactctggagtccgctaccagctcccagacatctgtgtacttctgtgccatcagtg agtc SEQ ID NO: 1691 TRBV24/OR9-2*01-RIGHT atacagtgtctctcgacaggcacaggctaaattctccctgtccctagagtctgccatccccaaccagacagctctttacttctgtgccaccagtg atttg SEQ ID NO: 1692 TRBV20/OR9-2*01-RIGHT acaagtttcccatcaaccatccaaacctgaccttctccgctctgacagtgaccagtgcccatcctgaagacagcagcttctacatctgcagtgct agaga SEQ ID NO: 1693 TRGV11*01-RIGHT ggtaagtaaaaatgctcacacttccacttccactttgaaaaataaagttcttagagaaagaagatgaggtggtgtaccactgtgcctgctggatt aggcac SEQ ID NO: 1694 TRBV7-8*02-RIGHT gcttctttgcagaaaggcctgagggatccgtctccactctgaagatccagcgcacacagaaggaggactccgccgtgtatctctgtgccagca gcttagc SEQ ID NO: 1695 TRBV7-3*02-RIGHT ggttcttgcagtcaggcctgagggatccgtctctactctgaagatccagcgcacagagcagggggactcagccgtgtatctccgtgccagcag cttaac SEQ ID NO: 1696 TRGV10*01-RIGHT aggcaagaaagaattctcaaactctcacttcaatccttaccatcaagtccgtagagaaagaagacatggccgtttactacctgtgctgcgtggtg ggtggc SEQ ID NO: 1697 TRGV9*02-RIGHT tgaggtggataggatacctgaaacgtctacatccactctcaccattcacaatgtagagaaacaggacatagctacctactactgtgccttgtgg gaggtg SEQ ID NO: 1698 TRDV3*02-RIGHT gacggttttctgtgaaacacattctgacccagaagcctttcacttggtgatctctccagtaaggactgaagacagtgccacttactactgtgcc tttag SEQ ID NO: 1699 TRDV2*02-RIGHT aatttccaaggtgacattgatattgcaaagaacctggctgtacttaagatacttgcaccatcagagagagatgaagggtcttactactgtgcct gtgaca SEQ ID NO: 1700 TRGV3*02-RIGHT agtattatactcatacacccaggaggtggagctggatattgagactgcaaaatctaattgaaaatgattctggggtctattactgtgccacctg ggacag SEQ ID NO: 1701 TRDV2*01-RIGHT tttccaaggtgacattgatattgcaaagaacctggctgtacttaagatacttgcaccatcagagagagatgaagggtcttactactgtgcctgtg acacc SEQ ID NO: 1702 TRBV19*02-RIGHT ggtacagcgtctctcgggagaagaaggaatcctttcctctcactgtgacatcggcccaaaagaacccgacagcttctatctctgtgccagtag tataga SEQ ID NO: 1703 TRAV14/DV4*01-RIGHT actcattgaatttccagaaggcaagaaaatccgccaaccttgtcatctccgcttcacaactgggggactcagcaatgtacttctgtgcaatgag agaggg SEQ ID NO: 1704 TRBV3-2*02-RIGHT gcttctcacctgactctccagacaagttcatttaaatcttcacatcaattccctggagcttggtgactctgctgtgtatttctgtgccagcagcca aga SEQ ID NO: 1705 TRGV10*02-RIGHT tggaggcaagaaagaattctcaaactctcacttcaatccttaccatcaagtccgtagagaaagaagacatggccgtttactactgtgctgcgtg ggatta SEQ ID NO: 1706 TRAV11*01-RIGHT caaatattttaaagaactgctggaaaagaaaaattttatagtgtttggaatatcgcagcctctcatctgggagattcagccacctacttctgtg ctttg SEQ ID NO: 1707 TRBV5-2*01-RIGHT aacttgcctaattgattctcagctcaccacgtccataactattactgagtcaaacacggagctaggggactcagccctgtatctctgtgccagca acttg SEQ ID NO: 1708 TRBV8-1*01-RIGHT ggaagggtacaatgtctctggaaacaagctcaagcattttccctcaaccctggagtctactagcaccagccagacctctgtacctctgtggcag tgcatc SEQ ID NO: 1709 TRAV38-1*01-RIGHT tctctgtgaacttccagaaagcagccaaatcccttcagtctcaagatctcagactcatagctgggggacactgcgatgtatttctgtgctttcatg aagca SEQ ID NO: 1710 TRBV22-1*01-RIGHT aggctacgtgtctgccaagaggagaaggggctatttcttctcagggtgaagttggcccacaccagccaaacagctttgtacttctgtcctggga gcgac SEQ ID NO: 1711 TRBV16*01-RIGHT gattttcagctaagtgcctcccaaattcaccctgtagccttgagatccaggctacgaagcttgaggattcagcagtgatttttgtgccagcagc caatc SEQ ID NO: 1712 TRBV30*01-RIGHT agaatctctcagcctccagaccccaggaccggcagttcatcctgagttctaagaagctccttctcagtgactctggcttctatctctgtgcctgga gtgt SEQ ID NO: 1713 TRAV3*01-RIGHT tttgaagctgatttaacaagagccaaacctccttccacctgaagaaaccatctgcccttgtgagcgactccgcttgtacttctgtgtgtgag agaca SEQ ID NO: 1714 TRAV26-1*01-RIGHT gcctctctgatcatcacagaagacagaaagtccagcaccttgatcctgccccacgctacgctgagagacactgctgtgtactattgcatcgtca gagttg SEQ ID NO: 1715 TRAV32*01-RIGHT aggctcactgtactgttgaataaaaatgctaaacatgtctccctgcatattacagccacccaaccaggagactcattcctgtacttctgtgcagt gagaa SEQ ID NO: 1716 TRAV33*01-RIGHT gcaaagcctgtgaactttgaaaaaaagaaaaagttcatcaacctcaccatcaattccttaaaactgactcagccaagtacttcgtgctctcag gaatcc SEQ ID NO: 1717 TRBV13*801-RIGHT gattctcagctcaacagttcagtgactatcattctgaactgaacatgagctccttggagctgggggactcagccctgtacttctgtgccagcagc ttagg SEQ ID NO: 1718 TRBV15*01-RIGHT acttccaatccaggaggccgaacacttctttctgctttcttgacatccgctcaccaggcctgggggacacagccatgtacctgtgtgccaccagc agaga SEQ ID NO: 1719 TRAV2*01-RIGHT agggacgatacaacatgacctatgaacggttctcttcatcgctgctcatcctccaggtgcgggaggcagatgctgtttactactgtgctgtg gagga SEQ ID NO: 1720 TRBV7-1*01-RIGHT ggttctctgcacagaggtctgagggatccatctccactctgaagttccagcgcacacagcagggggacttggctgtgtatctctgtgccagcag ctcagc SEQ ID NO: 1721 TRBV23-1*01-RIGHT gattctcatctcaatgccccaagaacgcaccctgcagcctggcaatcctgtcctcagaaccgggagacacggcactgtatctctgcgccagca gtcaatc SEQ ID NO: 1722 TRBV23/OR9-2*01-RIGHT gatgcacaagaagcgattctcatctcaatgccccaagaacccaccctgcagcctggcaatcctgtcctcggaaccgggagacaccgcactgta tctctgt SEQ ID NO: 1723 TRBVA*01-RIGHT tccctattgaaaatatttcctggcaaaaaatagaagttctctttggctctgaaatctgcaactccctttcaggtgtccctgtgtccttgtactgtca ctc SEQ ID NO: 1724 TRBVA/OR9-2*01-RIGHT tccctgttgaaaatatttcccggcaaaaaacagaagttccctttggctctgaaatctgcaaagccctttcagatgtccctgtgccttgtgccgtc actc SEQ ID NO: 1725 TRBV12-1*01-RIGHT gattctcagcacagatgcctgatgtatcattctccactctgaggatccagcccatggaacccagggacttgggcctatatttctgtgccagcagc tttgc SEQ ID NO: 1726 TRBV26/OR9-2*01-RIGHT ggtatcatgtttcttgaaatactatagcatcttttctcctgaccctgaagtctgctagcaccaaccagacatgtgtgtatctctgcgccagcagttc atc SEQ ID NO: 1727 TRGV9*01-RIGHT tgaggtggataggatacctgaaacgtctacatccactctcaccattcacaatgtagagaaacaggacatagctacctactactgtgccttgtgg gaggtg SEQ ID NO: 1728 TRGVB*01-RIGHT cttgaggcaagaacaaattttcaaatgtctacttcagtctttaccataaacttcataggaaaggaagatgaggccatttactactgcactgctta ggacc SEQ ID NO: 1729 TRBV7-3*01-RIGHT ggttctttgcagtcaggcctgagggatccgtctctactctgaagatccagcgcacagagcggggggactcagccgtgtatctctgtgccagcag cttaac SEQ ID NO: 1730 TRBV7-9*01-RIGHT ggttctctgcagagaggcctaagggatctttctccaccttggagatccagcgacacgagcagggggactcggccatgtatctctgtgccagcag cttagc SEQ ID NO: 1731 TRBV7-2*01-RIGHT gcttctctgcagagaggactgggggatccgtctccactctgacgatccagcgcacacagcaggaggactcggccgtgtatctctgtgccagca gcttagc SEQ ID NO: 1732 TRBV7-2*02-RIGHT gcttctctgcagagaggactggggaatccgtctccactctgacgatccagcgcacacagcaggaggactcggccgtgtatctctgtgccagca gcttagc SEQ ID NO: 1733 TRBV7-7*01-RIGHT ggttctctgcagagaggcctgagggatccatctccactctgacgattcagcgcacagagcagcgggactcagccatgtatcgctgtgccagca gcttagc SEQ ID NO: 1734 TRBV7-8*01-RIGHT gcttctttgcagaaaggcctgagggatccgtctccactctgaagatccagcgcacatagcaggaggactccgccgtgtatctctgtgccagcag cttagc SEQ ID NO: 1735 TRBV17*01-RIGHT aacgattcacagctgaaagacctaacggaacgtcttccacgctgaagatccatcccgcagagccgagggactcagccgtgatctctacagta gcggtgg SEQ ID NO: 1736 TRBV5-8*01-RIGHT agattttcaggtcgccagttccctaattatagctctgagctgaatgtgaacgccttggagctggaggactcggccctgtatctctgtgccagcag ttgg SEQ ID NO: 1737 TRBV5-7*01-RIGHT caattctcaggtcaccagttccctaactatagctctgagctgaatgtgaacgccttgttgctaggggactcggccctctatctctgtgccagcagc ttgg SEQ ID NO: 1738 TRBV5-6*01-RIGHT cgattctcaggtcaccagttccctaactatagctctgagctgaatgtgaacgccttgttgctgggggactcggccctctatctctgtgccagcagc ttgg SEQ ID NO: 1739 TRBV5-5*01-RIGHT cgattctcagctcgccagttccctaactatagctctgagctgaatgtgaacgccttgttgctgggggactcggccctgtatctctgtgccagcagc ttgg SEQ ID NO: 1740 TRBV5-4*01-RIGHT agattctcaggtctccagttccctaattatagctctgagctgaatgtgaacgccttggagctggacgactcggccctgtatctctgtgccagcag tttgg SEQ ID NO: 1741 TRBV-1*01-RIGHT cgattctcagggcgccagttctctaactctcgctctgagatgaatgtgagcaccttggagctgggggactcggccctttatctttgcgccagcag cttgg SEQ ID NO: 1742 TRBV3-1*01-RIGHT gcttctcacctaaatctccagacaaagctcacttaaatcttcacatcaattccctggagcttggtgactctgctgtgtatttctgtgccagcagcc aaga SEQ ID NO: 1743 TRBV1*01-RIGHT acttcacacctgaatgccctgacagctctcgcttataccttcatgtggtcgcactgcagcaagaagactcagctgcgtatctctgcaccagcagc caaga SEQ ID NO: 1744 TRBV5-3*01-RIGHT cgattctcagggcgccagttccatgactgttgctctgagatgaatgtgagtgccttggagctgggggactcggccctgtatctctgtgccagaag cttgg SEQ ID NO: 1745 TRBV5-3*02-RIGHT cgattctcagggcgccagttccatgactattgctctgagatgaatgtgagtgccttggagctgggggactcggccctgtatctctgtgccagaag cttgg SEQ ID NO: 1746 TRBV9*01-RIGHT cgattctccgcacaacagttccctgacttgcactctgaactaaacctgagctctctggagctgggggactcagctttgtatttctgtgccagcagc gtag SEQ ID NO: 1747 TRBV3-2*01-RIGHT gcttctcacctgactctccagacaaagctcatttaaatcttcacatcaattccctggagcttggtgactctgctgtgtatttctgtgccagcagcca aga SEQ ID NO: 1748 TRBV2*01-RIGHT aattctcagttgaaaggcctgatggaccaaatttcactctgaagatccggtccacaaagctggaggactcagccatgtacttctgtgccagcag tgaagc SEQ ID NO: 1749 TRBV4-3*01-RIGHT gcttctcacctgaatgccccaacagctctcacttattccttcacctacacaccctgcagccagaagactcggccctgtatctctgcgccagcagc caaga SEQ ID NO: 1750 TRBV4-1*01-RIGHT gcttctcacctgaatgccccaacagctctctcttaaaccttcacctacacgccctgcagccagaagactcagccctgtatctctgcgccagcagc caaga SEQ ID NO: 1751 TRBV4-2*01-RIGHT gcttctcacctgaatgcccaacagctctcacttattccttcacctacacaccctgcagccagaagactcggccctgtatctctgtgccagcagc caaga SEQ ID NO: 1752 TRAV34*01-RIGHT aagataactgccaagttggatgagaaaaagcagcaaagttccctgcatatcacagcctcccagcccagccatgcaggcatctacctctgtgga gcagaca SEQ ID NO: 1753 TRBV28*01-RIGHT ggtacagtgtctcagagagaagaaggagcgcttctccctgattctggagtccgccagcaccaaccagacatctatgtacctctgtgccagcag tttatg SEQ ID NO: 1754 TRBV20-1*01-RIGHT acaagtttctcatcaaccatgcaagcctgaccttgtccactctgacagtgaccagtgcccatcctgaagacagcagcttctacatctgcagtgct agaga SEQ ID NO: 1755 TRBV20/OR9-2*03-RIGHT acaagtttcccatcaaccatccaaacctgaccttctccgctctgacagtgaccagtgcccatcctgaagacagcagcttctacatctgcagtgct agaga SEQ ID NO: 1756 TRBV6-6*02-RIGHT gaatggctacaacgtctccagatcaaccacagaggatttcccgctcaggctggagttggctgctccctcccagacatctgtgacttctgtgcca gcagt SEQ ID NO: 1757 TRBV6-6*01-RIGHT gctacaacgtctccagatcaaccacagaggatttcccgctcaggctggagttggctgctccctcccagacatctgtgtacttctgtgccagcagt tactc SEQ ID NO: 1758 TRBV6-5*01-RIGHT gctacaatgtctccagatcaaccacagaggatttcccgctcaggctgctgcggctgctccctcccagacatctgtgtacttctgtgccagcagtt actc SEQ ID NO: 1759 TRBV6-8*01-RIGHT gctacaatgtctctagattaaacacagaggatttcccactcaggctggtgtcggctgctccctcccagacatctgtgtacttgtgtgccagcagtt actc SEQ ID NO: 1760 TRBV6-9*01-RIGHT gctacaatgtatccagatcaaacacagaggatttcccgctcaggctggagtcagctgctccctcccagacatctgtatacttctgtgccagcagt tattc SEQ ID NO: 1761 TRBV6-7*01-RIGHT gctacaatgtcttcagatcaaacacagaggatttccccctcaagctggagtcagctgctccctctcagacttctgtttacttctgtgccagcagtt actc SEQ ID NO: 1762 TRBV12-3*01-RIGHT gattctcagctaagatgcctaatgcatcattctccactctgaagatccagccctcagaacccagggactcagctgtgtacttctgtgccagcagt ttagc SEQ ID NO: 1763 TRBV12-4*01-RIGHT gattctcagctaagatgcctaatgcatcattctccactctgaagatccagccctcagaacccagggactcagctgtgacttctgtgccagcagt ttagc SEQ ID NO: 1764 TRBV12-5*01-RIGHT gattctcagcagagatgcctgatgcaactttagccactctgaagatccagccctcagaacccagggactcagctgtgtatttttgtgctagtggt ttggt SEQ ID NO: 1765 TRBV12-2*01-RIGHT gattctcagctgagaggcctgatggatcattctctactctgaagatccagcctgcagagcagggggactcggccgtgtatgtctgtgcaagtcg cttagc SEQ ID NO: 1766 TRBV6-1*01-RIGHT gctacaatgtctccagattaaacaaacgggagttctcgctcaggctggagtcggctgctccctcccagacatctgtgtacttctgtgccagcagt gaagc SEQ ID NO: 1767 TRBV7-4*01-RIGHT ggttctctgcagagaggcctgagagatccgtctccactctgaagatccagcgcacagagcagggggactcagctgtgtatctctgtgccagca gcttagc SEQ ID NO: 1768 TRBV7-5*01-RIGHT tcaattctccacagagaggtctgaggatctttctcccacctgaagatccagcgcacagagcaagggcgactcggctgtgtatctctgtgccagaa gcttag SEQ ID NO: 1769 TRAV20*01-RIGHT aaagaaaggctaaaagccacattaacaaagaaggaaagctttctgcacatcacagcccctaaacctgaagactcagccacttatctctgtgct gtgcagg SEQ ID NO: 1770 TRBV11-1*01-RIGHT gattttctgcagagaggctcaaaggagtagactccactctcaagatccagcctgcagagcttggggactcggccatgtatctctgtgccagcag cttagc SEQ ID NO: 1771 TRAV15*01-RIGHT acattttaaagaagcgcttggaaaagagaagttttatagtgttttgaatatgctggtctctcatcctggagattcaggcacctacttctgtgcttt gagg SEQ ID NO: 1772 TRAV7*01-RIGHT aaaggaagactaaatgctacattactgaagaatggaagcagcttgtacattacagccgtgcagcctgaagattcagccacctatttctgtgctg tagatg SEQ ID NO: 1773 TRAV16*01-RIGHT gcttcactgctgaccttaacaaaggcgagacatctttccacctgaagaaaccatttgctcaagaggaagactcagccatgtattactgtgctct aagtgg SEQ ID NO: 1774 TRAV6*01-RIGHT agactgaaggtcacctttgataccacccttaaacagagtttgtttcatatcacagcctcccagcctgcagactcagctacctacctctgtgctcta gaga SEQ ID NO: 1775 TRBV19*01-RIGHT ggtacagcgtctctcgggagaagaaggaatcctttcctctcactgtgacatcggcccaaaagaacccgacagctttctatctctgtgccagtag tataga SEQ ID NO: 1776 TRAV14/DR4*02-RIGHT actcattgaatttccagaaggcaagaaaatccgccaaccttgtcatctccgcttcacaactgggggactcagcaatgtatttctgtgcaatgag agaggg SEQ ID NO: 1777 TRAV9-1*01-RIGHT gttttgaagccatgtaccgtaaagaaaccacttctttccacttggagaaagactcagttcaagagtcagactccgctgtgtacttctgtgctctg agtga SEQ ID NO: 1778 TRAV9-2*01-RIGHT gtttgaagccacataccgtaaagaaaccacttctttccacttggagaaaggctcagttcaagtgtcagactcagcggtgtacttctgtgctctg agtga SEQ ID NO: 1779 TRAV1-1*01-RIGHT gtttttcttcattccttagtcgctctgatagttatggttacctccttctacaggagctccagatgaaagactctgccccttacttctgcgctgtgaga ga SEQ ID NO: 1780 TRAV38-8*01-RIGHT ttctctgtgaacttccagaaagcagccaaatccttcagtctcaagatctcagactcacagtgggggatgccgcgatgtatttctgtgcttatag gagcg SEQ ID NO: 1781 TRAV19*01-RIGHT attcttggaacttccagaaatccaccagttccttcaacttcattatcacagcctcacaagtcgtggactcagcagtatacttctgtgctctgagtg aggc SEQ ID NO: 1782 TRAV30*01-RIGHT aaaatatctgcttcatttaatgaaaaaaagcagcaaagctccctgtaccttacggcctcccagctcagttactcaggacctacttctgcggca cagaga SEQ ID NO: 1783 TRGV7*01-RIGHT agtattttacttatgcaagcatgaggaggagctggaaattgatactgcaaaatctaattgaaaatgattctggatctattactgtgccacctggg acagg SEQ ID NO: 1784 TRGV1*01-RIGHT aaagtatgacactggaagcacaaggagcaattggaatttgagactgcaaaatctaattaaaaatgattctgggttctattactgtgccacctgg gacagg SEQ ID NO: 1785 TRGV3*01-RIGHT gtattatactcatacacccaggaggtggagctggatattgagactgcaaaatctaattgaaaatgattctggggtctattactgtgccacctgg gacagg SEQ ID NO: 1786 TRGV5*01-RIGHT gtattatactcatacacccaggaggtggagctggatattgatactacgaaatctaattgaaaatgattctggggtctattactgtgccacctggg acagg SEQ ID NO: 1787 TRGV8*01-RIGHT gtatcatacttatgcaagcacagggacgagccttaaatttatactggaaaatctaattgaacgtgactctggggtctattactgtgccacctggg atagg SEQ ID NO: 1788 TRGV4*01-RIGHT gtatgatacttatggaagcacaaggaagaacttgagaatgatactgcgaaatcttattgaaaatgactctggagtctattacgtgccacctgg gatggg SEQ ID NO: 1789 TRGV2*01-RIGHT gtattatacttacgcaagcacaaggaacaacttgagattgatactgcgaaatctaattgaaaatgactctggggtctattactgtgcacctgg gacggg SEQ ID NO: 1790 TRGV5P*02-RIGHT gtattatactcatacaccgaggaggtggagctggaatttgagactgcaaaatctaattgaaaatgattctggggtttattactgtgccacctgg ggcagg SEQ ID NO: 1791 TRAV21*01-RIGHT aagacttaatgcctcgctggataaatcatcaggacgtagtactttatacattgcagcttctcagcctggtgactcagccacctacctctgtgctgt gagg SEQ ID NO: 1792 TRBV29/OR9-2*01-RIGHT acaagtttcccatcagccgcccaaacctaacattctcaactctgactgtgagcaacaggagacctgaagacagcagcatatacctctgcagcg ttgaaga SEQ ID NO: 1793 TRAV37*01-RIGHT agattcacagccaggcttaaaaaaggagaccagcacatttccctgcacatacaggattcccagctccatgactcaaccacattcttctgcgca gcaagca SEQ ID NO: 1794 TRBV21/OR9-2*01-RIGHT gattttcagcccaatgcccccaaaactcaccctgtaccttggagatccagtccacggagtcaggagacacagcacggtatttctgtgccaacag caaagc SEQ ID NO: 1795 TRBV21-1*01-RIGHT gatttttagcccaatgctccaaaaactcatcctgtaccttggagatccagtccacggagtcaggggacacagcactgtatttctgtgccagcag caaagc SEQ ID NO: 1796 TRAVB-6*01-RIGHT gttttgaggctgaatttaacaagagtcaaacttccttccacttgaggaaaccctcagtccatataagcgacacggctgagtacttctgtgctgtg agtga SEQ ID NO: 1797 TRAV8-3*01-RIGHT gctttgaggctgaatttaagaggatcaatcttccttcaatctgaggaaaccctctgtgcattggagtgatgctgctgagtacttctgtgctgtgg gtgc SEQ ID NO: 1798 TRBV29-1*01-RIGHT acaagtttcccatcagccgcccaaacctaacattctcaactctgactgtgagcaacatgagccctgaagacagtagcatatatctctgcagcgt tgaaga SEQ ID NO: 1799 TRBV25/OR9-2*01-RIGHT agtcaacagtctccagaataaggatagagcgttttcccctgaccctggagtctgccagcccctcacatacctctcagtacctctgtgccagcagt gaata SEQ ID NO: 1800 TRBV25-1*01-RIGHT agtcaacagtctccagaataaggacggagcattttcccctgaccctggagtctgccaggccctcacatacctctcagtacctctgtgccagcag tgaata SEQ ID NO: 1801 TRAV35*01-RIGHT aagactgactgctcagtttggtataaccagaaaggacagcttcctgaatatctcagcatccatacctagtgatgaggcatctacttctgtgctg ggcag SEQ ID NO: 1802 TRAV25*01-RIGHT gaaaagactgacatttcagtttggagaagcaaaaaagaacagctccctgcacatcacagccacccagactacagatgtaggaacctacttct gtgcaggg SEQ ID NO: 1803 TRAV12-2*01-RIGHT aggtttacagcacagctcaataaagccagccagtatgtttctctgctcatcagagactccccagcccagtgattcagccacctacctctgtgccgt gaaca SEQ ID NO: 1804 TRAV12-1*01-RIGHT aggtttacagcacagctcaatagagccagccagtatatttccctgctcatcagagactccaagctcagtgattcagccacctacctctgtgtggt gaaca SEQ ID NO: 1805 TRAV12-3*01-RIGHT aggtttacagcacaggtcgataaatccagcaagtatatctccttgttcatcagagactcacagcccagtgattcagccacctacctctgtgcaat gagcg SEQ ID NO: 1806 TRAV23/DV6*01-RIGHT agattcacaatctccttcaataaaagtgccaagcagttctcattgcatatcatggattcccagcctggagactcagccacctacttctgtgcagc aagca SEQ ID NO: 1807 TRAV22*01-RIGHT agattaagcgccacgactgtcgctacggaacgctacagcttattgtacatttcctcttcccagaccacagactcaggcgtttatttctgtgctgtg gagc SEQ ID NO: 1808 TRAV41*01-RIGHT aagattaattgccacaataaacatacaggaaaagcatagctccctgcacatcacagcctcccatcccagagactctgccgtctacatctgtgct gtcaga SEQ ID NO: 1809 TRAV39*01-RIGHT cgattaatggcctcacttgataccaaagcccgtctcagcaccctccacatcacagctgccgtgcatgacctctctgccacctacttctgtgccgt ggaca SEQ ID NO: 1810 TRAV36/DV7*01-RIGHT agactaagtagcatattagataagaaagaactttccagtatcctgaacatcacagccacccagaccggagactcggccatctacctctgtgct gtggagg SEQ ID NO: 1811 TRAV29/DV5*01-RIGHT agattcactgtcttcttaaacaaaagtgccaagcacctctctctgcatattgtgccctcccagcctggagactctgcagtgtacttctgtgcagca agcg SEQ ID NO: 1812 TRAV27*01-RIGHT aagagactaacctttcagtttggtgatgcaagaaaggacagttctctccacatcactgcagcccagcctggtgatataggcctctacctctgtg caggag SEQ ID NO: 1813 TRBV6-4*01-RIGHT gttatagtgtctccagagcaaacacagatgatttccccctcacgttggcgtctgctgtaccctctcagacatgtgtacttctgtgccagcagtg actc SEQ ID NO: 1814 TRBV10-1*01-RIGHT gctacagtgtctctagatcaaacacagaggacctccccctcactctggagtctgctgcctcctcccagacatctgtatatttctgcgccagcagt gagtc SEQ ID NO: 1815 TRBV10-2*01-RIGHT gctatgttgtctccagatccaagacagagaatttccccctcactctggagtcagctaccgctcccagacatctgtgtatttctgcgccagcagt gagtc SEQ ID NO: 1816 TRBV6-2*01-RIGHT gctacaatgtctccagattaaaaaaacagaatttcctgctggggttggagtcggctgctccctcccaaacatctgtgtacttctgtgccagcagt tactc SEQ ID NO: 1817 TRBV10-3*01-RIGHT gctatagtgtctctagatcaaagacagaggatttcctcctcactctggagtccgctaccagctcccagacatctgtgtacttctgtgccatcagttg agtc SEQ ID NO: 1818 TRAV24*01-RIGHT ggacgaataagtgccactcttaataccaaggagggttacagctatttgtacatcaaaggatcccagcctgaagactcagccacatcctctgt gccttta SEQ ID NO: 1819 TRBV14*01-RIGHT gattcttagctgaaaggactggagggacgtattctactctgaaggtgcagcctgcagaactggaggattctggagtttatttctgtgccagcag ccaaga SEQ ID NO: 1820 TRBV24-1*01-RIGHT atacagtgtctctcgacaggcacaggctaaattctccctgtccctagagtctgccatccccaaccagacagctctttacttctgtgccaccagtg atttg SEQ ID NO: 1821 TRBV24/OR9-2*03-RIGHT agtgtctctgacaggaacaggctaaattctccctgtccctagagcctgccacccccaaccagacagcttctaggttacttcagtgccaccagtg atttc SEQ ID NO: 1822 TRAV8-2*01-RIGHT gttttgaggctgaatttaagaagagtgaaacctccttccacctgacgaaaccctgacgaaaccctcagcccatatgagcgacgcggctgagtacttctgtgttgtg agtga SEQ ID NO: 1823 TRAV8-4*01-RIGHT gttttgaggctgaatttaagaagagtgaaacctccttccacctgacgaaaccctcagcccatatgagcgacgcggctgagtacttctgtgctgt gagtga SEQ ID NO: 1824 TRBV22/OR9-2*01-RIGHT ggctacggtgtctcccgagaggagaaggggctgtttcttctcatggtgaagctggcccacaccagccaaacagctctgtacttctgtcctggga gtgcac SEQ ID NO: 1825 TRAV26-2*01-RIGHT ggcctctctggcaatcgctgaagacagaaagtccagtaccttgatcctgcaccgtgctaccttgagagatgctgctgtgtactactgcatcctga gagac SEQ ID NO: 1826 TRBV11-2*01-RIGHT gattttctgcagagaggctcaaaggagtagactccactctcaagatccagcctgcaaagcttgaggactcggccgtgtatctctgtgccagcag cttaga SEQ ID NO: 1827 TRBV11-3*01-RIGHT gattttctgcagagaggctcaaaggagtagactccactctcaagatccagcctgcagagcttggggactcggccgtgtatctctgtgccagcag cttaga SEQ ID NO: 1828 TRAV8-1*01-RIGHT gctttgaggctgaatttataaagagtaaattctcctttaatctgaggaaaccctctgtgcagtggagtgacacagctgagtacttctgtgccgtg aatgc SEQ ID NO: 1829 TRBV7-5*02-RIGHT caattctccacagagaggtctgaggatctttctccacctgaagatccagcgcacagagcaagggcgactcggctgtgtatctctgtgtcagaag cttagc SEQ ID NO: 1830 TRBV7-6*01-RIGHT ggttctctgcagagaggcctgagggaatccatctccactctgacgatccagcgcacagagcagcgggactcggccatgtatcgctgtgccagca gcttagc SEQ ID NO: 1831 TRGV11*02-RIGHT gataagtaaaaatgctcacacttccacttccactttgaaaataaagttcttagagaaagaagatgaggtggtgtaccactgtgcctgctggatt aggcac SEQ ID NO: 1832 TRAV17*01-RIGHT agattaagagtcacgcttgacacttccaagaaaagcagttccttgttgatcacggcttcccgggcagcagacactgcttcttacttctgtgctac ggacg SEQ ID NO: 1833 TRBV27*01-RIGHT ggtacaaagtctctcgaaaagagaagaggaatttccccctgatcctggagtcgcccagccccaaccagacctctctgtacttctgtgccagcag tttatc SEQ ID NO: 1834 TRDV1*01-RIGHT attctgtcaacttcaagaaagcagcgaaatccgtcgccttaaccatttcagccttacagctagaagattcagcaaagtacttttgtgctcttggg gaact SEQ ID NO: 1835 TRBV18*01-RIGHT gattttctgctgaatttcccaaagagggccccagcatcctgaggatccagcaggtagtgcgaggagattcggcagcttatttctgtgccagctc accacc SEQ ID NO: 1836 TRAV5*01-RIGHT agactcactgttctattgaataaaaaggataaacatctgtctctgcgcattgcagacacccagactggggactcagctatctacttctgtgcag agagta SEQ ID NO: 1837 TRAV13-2*01-RIGHT agagtcaccgttttattgaataagacagtgaaacatctctctctgcaaattgcagctactcaacctggagactcagcgtctacttttgtgcaga gaata SEQ ID NO: 1838 TRDV2*03-RIGHT tttccaaggtgacattgatattgcaaagaacctggctgtacttaagatacttgcaccatcagagagagatgaagggtcttactactgtgccgtg acacc SEQ ID NO: 1839 TRAV1-2*01-RIGHT gtttttcttcattccttagtcggtctaaagggtacagttacctccttttgaaggagctccagatgaaagactctgcctcttacctctgtgctgtgag aga SEQ ID NO: 1840 TRDV3*01-RIGHTS gacggttttctgtgaaacacattctgacccagaaagcctttcacttggtgatctctccagtaaggactgaagacagtgccacttactactgtgcc tttag SEQ ID NO: 1841 TRAV31*01-RIGHT tattctgtgagcttccagaaaacaactaaaactattcagcttatcatatcatcatcacagccagaagacctgcaacatatttctgttgtctcaaa gagcc SEQ ID NO: 1842 TRAV10*01-RIGHT agatatacagcaactctggatgcagacacaaagcaaagctctctgcacatcacagcctcccagctcagcgattcagcctcctacatctgtgtg gtgagcg SEQ ID NO: 1843 TRAV28*01-RIGHT gaagactaaaatccgcagtcaaagctgaggaactttatggccacctatacatcagattcccagcctgaggactcagctatttacttctgtgctgt ggga SEQ ID NO: 1844 TRAV40*01-RIGHT aaaacttcggaggcggaaatattaaagacaaaaactcccccattgtgaaatattcagtccaggtatcagactcagccgtgtactacgtcttct gggaga SEQ ID NO: 1845 TRGV6*02-RIGHT gcatgatacttatggaagtagaaggataagctggaaatttatacctccaaaactaaatgaaaatgcctctggggtctattactgtgccacctag gacagg SEQ ID NO: 1846 TRAV18*01-RIGHT gttttcaggccagtcctatcaagagtgacagttccttccacctggagaagccctcggtgcagctgtcggactctgccgtgtactactgcgctctg agaga SEQ ID NO: 1847 TRBV26*01-RIGHT ggtatcatgtttcttgaaatactatagcatcttttcccctgaccctgaagtctgccagcaccaaccagacatctgtgtatctctatgccagcagttc atc SEQ ID NO: 1848 TRBV8-2*01-RIGHT agaggggtactgtgtttcttgaaacaagcttgagcatttccccaatcctggcatccaccagcaccagccagacctatctgtaccactgtggcag cacatc SEQ ID NO: 1849 TRGVA*01-RIGHT agataaaatcatagccaaggatggcagcagctctatcttggcagtactgaagttggagacaggcatcgagggcatgaactactgcacaacct gggccctg SEQ ID NO: 1850 TRAV4*01-RIGHT gcctccctgtttatccctgccgacagaaagtccagcactctgagcctgccccgggtttccctgagcgacactgctgtgtacctactgcctcgtgggt gaca SEQ ID NO: 1851 TRAV8-7*01-RIGHT aggctgaatttaagaagagcgaaacctccttctacctgaggaaaccatcaacccatgtgagtgatgctgctgagtacttctgtgctgtgggtga caggag SEQ ID NO: 1852 TRAV13-1*01-RIGHT cgaattgctgttacattgaacaagacagccaaacatttctccctgcacatcacagagacccaacctgaagactcggctgtctacttctgtgcag caagta SEQ ID NO: 1853 TRBVB*01-RIGHT gactcgagaccctctgcagcagcagcctatcagtgcagccatatcctctctgagcggatatgacaaaccccagggttgaagcgacctaacct atgagcc SEQ ID NO: 1854 TRAV8-5*01-RIGHT tggacacttatcacttccccaatcaatacccctgtgatttcctatgcctgtctttactttaatctcttaatcctgtcagctgaggaggatgtatgtca cc SEQ ID NO: 1855 TRBV16*02-RIGHT gattttcagctaagtgcctcccaaattcaccctgtagccttgagatccaggctacgaagcttgaggattcagcagtgtatttttgtgccagcagc caatc SEQ ID NO: 1856 TRBV26/OR9-2*02-RIGHT ggtatcatgtttcttgaaatactatagcatcttttctcctgaccctgaagtctgctagcaccaaccagacatgtgtgtatctctgcgccagcagttc atc SEQ ID NO: 1857 TRBV7-3*03-RIGHT ggttctttgcagtcaggcctgagggatccgtctctactctgaagatccagcgcacagagcagggggactcagccgcgtatctccgtgccagca gcttaac SEQ ID NO: 1858 TRBV7-9*03-RIGHT tgatcggttctctgcagagaggcctaagggatctttctccaccttggagatccagcgcacagagcagggggactggccatgtatctctgtgcc agcagc SEQ ID NO: 1859 TRBV9*02-RIGHT cgattctccgcacaacagttccctgacttgcazctctgaactaaacctgagctctctggagctgggggactcagctttgtatttctgtgccagcagc gtag SEQ ID NO: 1860 TRBV29/OR9-2*02-RIGHT acaagtttcccatcagccgcccaaacctaacattctcaactctgactgtgagcaacaggagacctgaagacagcagcatatacctctgcagcg ttgaaga SEQ ID NO: 1861 TRAV8-6*02-RIGHT gttttgaggctgaatttaacaagagtcaaacttccttccacttgaggaaaccctcagtccatataagcgacacggctgagtacttctgtgctgtg agtga SEQ ID NO: 1862 TRBV6-4*02-RIGHT gttatagtgtctccagagcaaacacagatgatttccccctcacgttggcgtctgctgtaccctctcagacatctgtgtacttctgtgccagcagtg actc SEQ ID NO: 1863 TRBV10-1*02-RIGHT agatggctacagtgtctctagatcaaacacagaggacctccccctcactctggagtctgctgcctcctcccagacatctgtatatttctgcgcca gcagt SEQ ID NO: 1864 TRBV6-3*01-RIGHT gctacaatgtctccagattaaaaaaacagaatttcctgctggggttggagtcggctgctccctcccaaacatctgtgtacttctgtgccagcagt tactc SEQ ID NO: 1865 TRAJ1*801 aatagagacacggggcatggtatgaaagtattacctcccagttgcaatttggcaaaggaaccagagtttccacttctccccgtacgtctgccca tgccca SEQ ID NO: 1866 TRAJ10*01 gaggcatcaaacactgtgatactcacgggaggaggaaacaaactcacctttgggacaggcactcagctaaaagtggaactcagtaagtatg agattctat SEQ ID NO: 1867 TRAJ11*01 tatggggatttgctatagtgtgaattcaggatacagcaccctcacctttgggaaggggactatgcttctagtctctccaggtacatgttgacccc atccc SEQ ID NO: 1868 TRAJ12*01 actgactaagaaacactgtgggatggatagcagctataaattgatcttcgggagtgggaccagactgctggtcaggcctggtaagtaaggtgt cagagag SEQ ID NO: 1869 TRAJ13*01 aaggcaggcattacagtgtgaattctgggggttaccagaaagttacctttggaattggaacaaagctccaagtcatcccaagtgagtccaattt cctatg SEQ ID NO: 1870 TRAJ13*02 aaaggcaggcattacagtgtgaattctgggggttaccagaaagttacctttggaactggaacaaagctccaagtcatcccaagtgagtccaat ttcctat SEQ ID NO: 1871 TRAJ14*01 tttgtcaggcagcacagtgctgtgatttatagcacattcatctttgggagtgggacaagattatcagtaaaacctggtaagtaggcaatatgtca ctaaa SEQ ID NO: 1872 TRAJ15*01 cagggcctcatttcacgtgccaaccaggcaggaactgctctgatctttgggaagggaaccaccttatcagtgagttccagtaagtacctgata attatt SEQ ID NO: 1873 TRAJ15*02 cagggcctcatttcactgtgccaaccaggcaggaactgctctgatctttgggaagggaacccacctatcagtgagttccagtaagtacctgata attatt SEQ ID NO: 1874 TRAJ16*01 tggtacaatagatcactgtgggttttcagatggccagaagctgctctttgcaaggggaaccatgttaaaggtggatcttagtaagtattattact aatga SEQ ID NO: 1875 TRAJ17*01 cctgtggtttttgctgggccttaaatcattgtgtgatcaaagctgcaggcaacaagctaacttttggaggaggaaccagggtgctagttaaacc aagtga SEQ ID NO: 1876 TRAJ18*01 aggggaccagcattgtgccgacagaggctcaaccctggggaggctatactttggaagaggaactcagttgactgtctggcctggtgagtgagt cgctttc SEQ ID NO: 1877 TRAJ19*01 ttttgcagaggacagatgtggctatcaaagattttacaatttcaccttggaaagggatccaaacataatgtcactccaagtaagtgagcagcc ttttgt SEQ ID NO: 1878 TRAJ2*01 tggtgtcacctacggtatgaatactggaggaacaattgataaactcacatttgggaaagggacccatgtatccattatatctggtgagtcatccc aggtg SEQ ID NO: 1879 TRAJ20*01 tgtaggcgacctcgcactgtggttctaacgactacaagctcagctttggagccggaaccacagtaactgtaagagcaagtaagtaagaaaga aaagtcca SEQ ID NO: 1880 TRAJ21*01 tgtaatgccaataaacatggtgtacaacttcaacaaattttactttggatctgggaccaaactcaatgtaaaaccaagtaagttatagttgccta gaaga SEQ ID NO: 1881 TRAJ22*01 gttgagcaaatcatagtgtttcttctggttctgcaaggcaactgacctttggatctgggacacaattgactgttttacctggtaggctgcctcaatt aaa SEQ ID NO: 1882 TRAJ23*01 aggatatgtaacacagtgtgatttataaccagggaggaaagcttatcttcggacagggaacggagttatctgtgaaacccagtaagtataa attgtatc SEQ ID NO: 1883 TRAJ23*02 gactggatgtgtttttgacaggatatgtaacacagtgtgatttataaccagggaggaaagcttatcttcggacagggaacggagctatctgtga aaccca SEQ ID NO: 1884 TRAJ24*01 gaggtgtttgtcacagtgtgacaattgacagctgggggaaattcgagtttggagcagggacccaggttgtggtcaccccaggtaagcccattc ctggagc SEQ ID NO: 1885 TRAJ24*02 gaggtgtttgtcacagtgtgacaactgacagctgggggaaattgcagtttggagcagggacccaggttgtggtcaccccaggtaagcccatt ccctgga SEQ ID NO: 1886 TRAJ25*01 atgctgagataatcactatgcagaaggacaaggcttctcctttatctttgggaaggggacaaggctgcttgtcaagccaagtaagtgacatata atttat SEQ ID NO: 1887 TRAJ26*01 ctgagcccagaaacactgtggggataactatggtcagaattttgtctttggtcccggaaccagattgtccgtgctgccctgtaagtacagttaag tggag SEQ ID NO: 1888 TRAJ27*01 caatagcactaaagactgtgtaacaccaatgcaggcaaatcaacctttggggatgggactacgctcactgtgaagccaagtaagttgtgttctt ctttgc SEQ ID NO: 1889 TRAJ28*01 agaaaggaaactctgtgcatactctggggctgggagttaccaactcactttcgggaaggggaccaaactctcggtcataccaagtaagttcttc tttctg SEQ ID NO: 1890 TRAJ29*01 ttatggaggaaatcactgtgggaattcaggaaacacacctcttgtctttggaaagggcacaagactttctgtgattgcaagtaagtgtttctagc catcc SEQ ID NO: 1891 TRAJ3*01 aaagaccttacccacagtgggggtacagcagtgcttccaagataatctttggatcagggaccagactcagcatccggccaagtaagtagaat gaagcagg SEQ ID NO: 1892 TRAJ30*01 gttatggtcccaatcacagtgtgaacagagatgacaagatcatctttggaaaagggacacgacttcatattctccccagtaagtgctgtttatgt gattt SEQ ID NO: 1893 TRAJ31*01 agtaaaggcaggaagtgctgtggaataacaatgccagactcatgtttggagatggaactcagctggtggtgaagcccagtaagtggccatgtt ttattga SEQ ID NO: 1894 TRAJ32*01 ggctctgaaggactgtgtgaattatggcggtgctacaaacaagctcatctttggaactggcactctgcttgctgtccagccaagtacgtaagta gtggca SEQ ID NO: 1895 TRAJ32*02 gtgattcagccacctacctctgtgccgatggtggtgctacaaacaagctcatctttggaactggcactctgcttgctgtccagccaaatatccag aaccc SEQ ID NO: 1896 TRAJ33*01 gttaaggtttttgtgtctgtgtggatagcaactatcagttaatctggggcgctgggaccaagctaattataaagccaggtaagtctcagagatgt gactg SEQ ID NO: 1897 TRAJ34*01 aggtttttgtagatctcagtatcactgtgtcttataacaccgacaagctcatctttgggactgggaccagattacaagtctttccaagt SEQ ID NO: 1898 TRAJ35*01 taaaagaatgagccattgtggataggctttgggaatgtgctgcattgcgggtccggcactcaagtgattgttttaccacgtaagtatatcttttct catt SEQ ID NO: 1899 TRAJ36*01 tactgggcagaaacactgtgtcaaactggggcaaacaacctcttctttgggactggaacgagactcaccgttattccctgtaagtccttacctct tgaca SEQ ID NO: 1900 TRAJ37*01 aaagtacagcattagagtgtggctctggcaacacaggcaaactaatctttgggcaagggacaactttacaagtaaaaccaggtaggtctgga tgtttcca SEQ ID NO: 1901 TRAJ37*02 ctcagcggtgtacttctgtgctcttcatggctctagcaacacaggcaaactaatctttgggcaagggacaactttacaagtaaaaccagatatc cagaac SEQ ID NO: 1902 TRAJ38*01 aaagctttctatgactgtgtaatgctggcaacaaccgtaagctgatttggggattgggaacaagcctggcagtaaatccgagtgagtcttcgtg ttaact SEQ ID NO: 1903 TRAJ39*01 cagccgaagatcactgtgtgaataataatgcaggcaacatgctcacctttggagggggaacaaggttaatggtcaaaccccgtgagtatctct gctgaat SEQ ID NO: 1904 TRAJ4*01 aagcaccatctgattgtgtgttttctggtggctacaataagctgatttttggagcagggaccaggctggctgtacacccatgtgagtatgaccct gcaag SEQ ID NO: 1905 TRAJ40*01 tatgttggtttatgtagagacacataacactgtgactacctcaggaacctacaaatacatctttggaacaggcaccaggctgaaggttttagca agt SEQ ID NO: 1906 TRAJ41*01 ttagggagaacgcactgtggaactcaaattccgggtatgcactcaacttcggcaaaggcacctcgctgttggtcacaccccgtgagtttttgtg gtttac SEQ ID NO: 1907 TRAJ42*01 agccccataggactgtgtgaattatggaggaagccaaggaaatctcatctttggaaaaggcatctaaactctctgttaaaccaagtaagtgttg gggattc SEQ ID NO: 1908 TRAJ43*01 ttgttagagcatgtattactgtgacaataacaatgacatgcgctttggagcagggaccagactgacagtaaaaccaagtaagttgggggaatg ggtcaat SEQ ID NO: 1909 TRAJ44*01 aggtttctgttatgaagcatctcacagtgtaaataccggcactgccagtaaactcacctttgggactggaacaagacttcaggtcacgctcggt SEQ ID NO: 1910 TRAJ45*01 agggttggcccagagtgtgtattcaggaggaggtgctgacggactcaccttggcaaagggactcatctaatcatccagccctgtaagtgcttt tgcctg SEQ ID NO: 1911 TRAJ46*01 aagctgctgacagccgtgagaagaaaagcagcggagacaagctgacttttgggaccgggactcgtttagcagttaggcccagtaagtctgag cagaaagt SEQ ID NO: 1912 TRAJ47*01 gtagaggagttgacgctgtgtggaatatggaaacaaactggtctttggcgcaggaaccattctgagagtcaagtcctgtgagtataaaacac actcaag SEQ ID NO: 1913 TRAJ47*02 gtgtactattgcatctcggccctggaatatggaaacaagctggtctttggcgcaggaaccattctgagagtcaagtcctatatccagaaccctg accctg SEQ ID NO: 1914 TRAJ48*01 atgacttagaacactgtgtatctaactttggaaatgagaaattaacctttgggactggaacaagactcaccatcatacccagtaagttcttcatc cttgg SEQ ID NO: 1915 TRAJ49*01 tgttgagcttcctatcacagtggaacaccggtaaccagttctatttgggacagggacaagtttgacggcattccaagtaagtcaaagaaaat tttcca SEQ ID NO: 1916 TRAJ5*01 tactgtgatgtaccagggtgtggacacgggcaggagagcacttacttttgggagtggaacaagactcccaagtgcaaccaagtaagtacccaa acttaggc SEQ ID NO: 1917 TRAJ50*01 taaaggtttggatggctgtgtgaaaacctcctacgacaaggtgatatttgggccagggacaagcttatcagtcattcccaagtaagtgtccctgg ggtgct SEQ ID NO: 1918 TRAJ51*01 aaactccctgaagcagggagatgcgtgacagctatgagaagctgatatttggaaaggagacatgacttaactgtgaagccaagcaagctgga aagacctaa SEQ ID NO: 1919 TRAJ52*01 gcctccagtgcagtgctaatgctggtggtactagctatggaaagctgacatttggacaagggaccatcttgactgtccatccaagtaagtgtaa caagac SEQ ID NO: 1920 TRAJ53*01 agccttctgtggctgtgagaatagtggaggtagcaactataaactgacatttggaaaaggaactctcttaacgtgaatccaagtaagtttgaa gggagt SEQ ID NO: 1921 TRAJ54*01 taaagcctcgtgctgtggtgtaattcagggagcccagaagctggtatttggccaaggaaccaggctgactatcaacccaagtaagtatgacag ggtgaag SEQ ID NO: 1922 TRAJ55*01 gaggatggatccctgttagtgacaagtgctggtaatgctcctgttggggaaaggggatgagtacaaaaataaatccaagtaagtgtggaggg acaagaag SEQ ID NO: 1923 TRAJ56*01 agatcctcgtgtcattgtgttatactggagccaatagtaagctgacatttggaaaaggaataactctgagtgttagaccaggtatgttttaatga atgtt SEQ ID NO: 1924 TRAJ57*01 aagcagtctgtgggggtgtaactcagggcggatctgaaaagctggtctttggaaagggaacgaaactgacagtaaacccatgtaagtctgaa taatgctt SEQ ID NO: 1925 TRAJ58*01 aagcccctcagcacagtgtttaagaaaccagtggctctaggttgacctttggggaaggaacacagctcacagtgaatcctggtaagtggagg ggagcatt SEQ ID NO: 1926 TRAJ59*01 atgtaaaggcagcagctcctgtgggaaggaaggaaacaggaaatttacatttggaatggggacgcaagtgagagtgaagctatctttaaacc aaaggtgt SEQ ID NO: 1927 TRAJ6*01 caggttttatcaaaggctgtcctcactgtgtgcatcaggaggaagctacatacctacatttggaagaggaaccagccttattgttcatccgtgta agt SEQ ID NO: 1928 TRAJ60*01 gtaaagggcctgggcactatgtgaagatcacctagatgctcaactttgggaaggggactgagttaattgtgagcctgggtgagtacctcaact ccagagg SEQ ID NO: 1929 TRAJ61*01 taaaggtgcccactcctgtgggtaccgggttaataggaaactgacatttggagccaacactagaggaatcatgaaactcagcaagtaatattt ggcagaa SEQ ID NO: 1930 TRAJ7*01 tgtaatacacttacacagtgtgactatgggaacaacagactcgcttttgggaaggggaaccaagtggtggtcataccaagtaagtgagctggg atcctcc SEQ ID NO: 1931 TRAJ8*01 tacagagttatgtcagagtgtgaacacaggctttcagaaacttgtatttggaactggcacccgacttctggtcagtccaagtaagtcaaatctg cagaaa SEQ ID NO: 1932 TRAJ9*01 cgcagtgcaaatcactgtgggaaatactggaggcttcaaaactatctttggagcaggaacaagactatttgttaaagcaagtaagttccatga aataacc SEQ ID NO: 1933 TRBJ1-1*01 ttttcaccttgacccctgtcactgtgtgaacactgaagctttcttggacaaggcaccagactcacagttgtaggtaagacatttttcaggttcttt tgc SEQ ID NO: 1934 TRBJ1-2*01 ttttagagtggctatattcttatgtgctaactatggctacaccttcggttcggggaccaggttaaccgttgtaggtaaggctgggggtctctagga gggg SEQ ID NO: 1935 TRBJ1-3*01 tttgaagtggccctgggaggctgtgctctggaaacaccatatattttggagagggaagttggctcactgttgtaggtgagtaagtcaaggctgg atagct SEQ ID NO: 1936 TRBJ1-4*01 ttccttccagtctttaatgttgtgcaactaatgaaaaactgttttttggcagtggaacccagctctctgtcttgggtatgtaaaagacttctttcgg gat SEQ ID NO: 1937 TRBJ1-5*01 tttgccacactcatgatgcactgtgtagcaatcagccccagcattttggtgatgggactcgactctccatcctaggtaagttggcagaatcaggg tggta SEQ ID NO: 1938 TRBJ1-6*01 ttatctaagcctctgcagctgtgctcctataattcacccctccactttgggaatgggaccaggctcactgtgacaggtatgggggctcccactcttg actc SEQ ID NO: 1939 TRBJ1-6*02 ttatctaagcctctgcagctgtgctcctataattcacccctccactttgggaacgggaccaggctcactgtgacaggtatgggggctccactcttg actc SEQ ID NO: 1940 TRBJ2-1*01 ttctgggcagcccctcccactgtgctcctacaatgagcagttcttcgggccagggacacggctcaccgtgctaggtaagaaagggggctccagg tgggag SEQ ID NO: 1941 TRBJ2-2*01 tgcgccagggtccccagggctgtgcgaacaccggggagctgttttttggagaaggctctaggctgaccgtactgggtaaggaggcggctggg gctccgga SEQ ID NO: 1942 TRBJ2-2P*01 agctgccccactctgagaggggctgtgctgagaggcgctgctgggcgtctgggcggaggactcctggttctgggtgctgggagagcgatgggg ctctcag SEQ ID NO: 1943 TRBJ2-3*01 ttttgtcctgggcctccaggctgtgagcacagatacgcagtattttggcccaggcacccggctgacagtgctcggtaagcgggggctcccgctg aagccc SEQ ID NO: 1944 TRBJ2-4*01 ttctgtgccgcgtctcggggctgtgagccaaaaacattcagtacttcggcgccgggacccggctctcagtgctgggaagctggggccgccggg ggaccg SEQ ID NO: 1945 TRBJ2-5*01 tttttgtgcggggctcgggggccgtgaccaagagacccagtacttcgggccaggcacgcggctcctggtgctcggtgagcgcgggctgctggg gcgcggg SEQ ID NO: 1946 TRBJ2-6*01 ttgcggggagtccccgggctgtgctctggggccaacgtcctgactttcggggccggcagcaggctgaccgtgctgggtgagttttcgcgggacc acccgg SEQ ID NO: 1947 TRBJ2-7*01 tttgcatgcgggggtgcacctccgtgctcctacgagcagtacttcgggccgggcaccaggctcacggtcacaggtgagattcggcgtctcccc accttc SEQ ID NO: 1948 TRBJ2-7*02 tttgcatgcggggatgcacctccgtgctcctacgagcagtacgtcgggccgggcaccaggctcacggtcacaggtgagattcgggcgtctcccc accttc SEQ ID NO: 1949 TRDJ1*01 ttttggaacgtcctcaagtgctgtgacatcgataaactcatctttggaaaaggaacccgtgtgactgtggaaccaagtaagtaactcattattta tctga SEQ ID NO: 1950 TRDJ2*01 tttttcgtaatgacgcctgtggtagtgctttgacagcacaactcttctttggaaagggaacacaactcatcgtggaaccaggtaagttatgcattt tact SEQ ID NO: 1951 TRDJ3*01 tgaggcactgtcataatgtgctcctgggacacccgacagatgttttcggaactggcatcaaactcttcgtggagccccgtgagttgatctttttc ctat SEQ ID NO: 1952 TRDJ4*01 atgagacatacaaaaaggtaatgccgccccagacccctgatctttggcaaaggaacctatctggaggtacaacaac SEQ ID NO: 1953 TRGJ1*01 ttttgatatggactgaatcactgtggaattattataagaaactcttggcagtggaacaacactggttgtcacaggtaagtatcggaagaatac aacatt SEQ ID NO: 1954 TRGJ1*02 tactgtgccttgtgggaggtgcttattataagaaactctttggcagtggaacaacacttgttgtcacaggt SEQ ID NO: 1955 TRGJ2*01 ttttgatatggactgaatcactgtggaattattataagaaactctttggcagtggaacaacacttgttgtcacaggtaagtatcggaagaataca acatt SEQ ID NO: 1956 TRGJP*01 ataaaggcttctcaggtggtgggcaagagttgggcaaaaaaatcaaggtatttggtcccggaacaaagcttatcattacaggtaagttttcttt aaattt SEQ ID NO: 1957 TRGJP1*01 gatttttctagaagcttagaccggtgtgataccactggttggttcaagatatttgctgaagggactaagctcatagtaacttcacctggtaagt SEQ ID NO: 1958 TRGJP2*01 gatttttgtagaagcttagaccagtgtgatagtagtgattggatcaagacgtttgcaaaagggactaggctcatagtaacttcgcctggtaagt

TABLE B1 SEQ ID NO Name Sequence SEQ ID NO: 239 IGHV(II)-1- CACACTTGAGCCCAGCCTTTCTGGGCCAACTCTCCATCTGTAGAGACACATCCAAGGCCCAGTTATCCCTGCAGCTGAGCTCCGTGAT 1*01 GGCCAAGGGCAGGGCCGCACATTCCCGTGGGA SEQ ID NO: 240 IGHV(II)-20- GCTTGTTGCTCATGTAGCTCAGCCATAGGAAGAGCTGCCCCGGCGGACATAGATCTGGAGGTGGCGACTGGACTCTTGAGGAGTG 1*01_IGHV(II)- GGTTGGAATTTTTGCTGCCTTCATGACCTGTGCAC 20-1*02 SEQ ID NO: 241 IGHV(II)-22- AATCCAACCCACTCCTCAAGAGTCCAGTCACCATCTCCAGATCCACATCCAAAAAACAGTTTCTCCTACAGCTGAGCTACCTTAACAA 1*01_IGHV(II)- GGAGTACACAACCATGATTTTTATACAAAAGA 23-2*01 SEQ ID NO: 242 IGHV(II)-26- CATCATGCACCCTCCACCCAGGTCCATGTCCCCATCAACAGTGACTCAACCAAGAGCCAGTTCTCTGTGAAGCTCAGCTCCATGACCA 2*01 CCTAGGACACGGCTGAGTATTACTGTGAAAGA SEQ ID NO: 243 IGHV(II)-28- GTGAAGGGAGCACAAATTACAACCCACTGCTCAAGAGTCCATATCCAGATCCAAGAAACAGTTCTTACAGCTGAGCTCTGTGCCCA 1*02_IGHV(II)- GTGAACACACAACTACGCATTTTTAAGCAAAAGA 28-1*03 SEQ ID NO: 244 IGHV(II)-30- TTACTCCCCTCTTCTCCAAGAGTCCAGTCACCATCTCCAGATCCATGTCCAAAAAGTAGTTCTTCTTACAGCTGAACTATGTGAGGAAC 1*01_IGHV(II)- AAACACATAGCCATGTATTTTAGAGCAAAAGA 30- 1*02_IGHV(II)- 30- 32*01_IGHV(II)- 30- 51*01 SEQ ID NO: 245 IGHV(II)-30- TTACAACCCACTTCTCAAGAGTCCATATCCGGATCCAAGAAACAGTTCTTACAGCTGAGCTCTGTGCCCAGTGAACACACAACTACG 21*01 CATTTTGAAGCAAAAGATGCAATGAAGGGCCTT SEQ ID NO: 246 IGHV(II)-30- TTACAACCCACTGCTCAAGAGTCCATAATCCAGATCCAAGAAACAGTTCTTACAGCTGAGCT CTGTGCCCAGTGAACACACAACTACG 41*01 CATTTTTAAGCAAAAGACGCAATGAAGGGCCTT SEQ ID NO: 247 IGHV(II)-30- TTACTCCCCTCTTCTCAAGAGTCCAGTCACCATCTCCAGATCCATGTCCAAAAAGTACTTCTTCTTACAGGTGAACTATGTGAGCAACA 51*02_IGHV(II)- AACACATAGCCATGTATTTTAGAGCAAAAGA 33-1*-1 SEQ ID NO: 248 IGHV(II)-31- TTACATCCCACTTCTCAAGAGTCCATATCCAGATCCAAGAAACAGTTCTTACAGCTGAGCTCTGTGCCCAGTGAACACACAACTACAC 1*01 ATTTTGAAGCAAAAGACGCAATGAAGGGCCTT SEQ ID NO: 249 IGHV(II)-40- AGCCTGGTGAAGCCCTTGCAAACCCCCTCACTCACCTGTGCTGCCTCTGGATTCTCTGTCACAATCAGTGCTTCCTG 1*01 SEQ ID NO: 250 IGHV(II)-43- CATGAAGGGAGCACAAATTCTAACCCACTCCTCAAGAGTCCAGTCACCACCTCCAGATCTATGTCCAAAAACAGCTCTTCGTATGGC 1*01 TGAGTGACATTAGCAACAAGCACACAGCCATGT SEQ ID NO: 251 IGHV(II)-43- CATGAAGGGAGCACAAATTCTACCCACTCCTCAAGAGTCCAGTCACCACCTCCAGATCTATGTCCAAAAACAGCTCTTCGTATGGC 1D*01 TGAGTGACATTAGCAACAAGCACACAACCATGT SEQ ID NO: 252 (IGHV(II)-44- ACGATGATCCATCTCTGCAGAGCCAACTCTCCTTCTCCAGAGATTCATCCAAGAAACAATTTTGACTATACCTGAGCTCTGTGACATC 2*01 TGAGGACATGGTTTGTATTACTGTGCAAGACA SEQ ID NO: 253 IGHV(II)-46- GACCTGAATAGCACACACTTACCCTCTGCCTCACCTACACTGTTACTGGCCACTCCGTCACAACCAGTCCTTACTAGTGGACCTGGAT 1*01 CTGCCGGCTCTCAGGGAGGGGCTGCAATGGAT SEQ ID NO: 254 IGHV(II)-49- ACGCAACCCACGCCTCAAGAGTCCAGTCACCATCTCFAGATCCACATCCAAAACACAGTTTCTTCTACAGCTGAGCTACCTGAGCAAC 1*01 GAGTACACAACCATGAATTTTTACACAAAAGA SEQ ID NO: 255 IGHV(II)-51 AATTCTAACCCACTCCTCATGAGCTCAGTCACCATCTCCAGATCCACGTCCAAGAACCAAATTTTCTTTTAGCTGAGTTCTGTGACCAA 2*01 CAATGCCACAACCTTGTATTACTGTGAGAGG SEQ ID NO: 256 IGHV(II)-53- ATTCCAACCCACTCCTCAAGAGTCCAGTCACCATCTCCAGATCCATGTCCAAAAAGCAGTTCTTCCTACAGCCGAGCTAAGTGAGTCA 1*01 CAAGCACACAGCCATGTATTTTTAACAAAAGA SEQ ID NO: 257 IGHV(II)-60- AAATTCCCACCCACTCCTTATGAATCCAGTCACCATCTCCAAATTCGGGTCCAAAAAACACTTGTTTTTACAGTGGAGCTATGTGAGC 1*-1 AACAAGCTCACAGCCATGTTTTAAAGAAGAGA SEQ ID NO: 258 IGHV(II)-62- ATTACTCCCCTTTCCTCAAGAGTCCAGTCACCATCCCCAGATCCATGTCCAAAAACAGTTCTTCCTACAGCTGAGCTACATGAGCAAC 1*-01 AATCACATAGCCATATATTTTTCAGCAATAGA SEQ ID NO: 259 IGHV(II)-65- TTCCAACCCACTCCTCAAGAGTCCAGTCACTATCTCCAGATCCACATCCAAAAAACAGTGTTTCCTGTAGCTGAGCTACCTGAGCAAC 1*01 AAGTACACAACCATGAATTTTAATACAAAAGA SEQ ID NO: 260 IGHV(II)-67- ATGCCTAGGTGTGAAGATCACACACTGACCTCACCCATGCTGTCTCTGGCCACTTCATCACAACCAATGCTTAATATTGGACGTGGAT 1*-1 CTGCCAGTCCCCGGGGAATGGGTTGAATGGAT SEQ ID NO: 261 IGHV(III)-11- GGCAGCAACAGGGAGAAATTCAAGAGGAAGTTCTTACATGCACCCTTACGTGCACGGTCTCACTGAGATCTTTACTTCCTTTATCAC 1*01 GTTTGTTCTGTAAATCACAACGAATGGTGCATT SEQ ID NO: 262 IGHV(III)-13- TGGGACTCTCCTTGAGTAAAAAGATGATTAACAATCCTCAAATACACTCAGTTCAGGAGATTCTCTTTAAGATGATTAACCTGAGA 1*01 GCTCAGGAAAAGTCCGTGTATTACTTTGAGGGA SEQ ID NO: 263 IGHV(III)-16- TCAGAGTTACTCTCCATGAGTACAAATAAATTAACAGTCCCAAGCGACACCTTTTCATGTGCAGTCTACCTTAAAGGGACCAAACTG 1*01 AAAGTCAAGGACAAGGCCTTGTAATACTGTGAG SEQ ID NO: 264 IGHV(III)-20- ACCAGAAGAATGCTATCATCATCTTTTCTGTTCTTTTGGAAGGAATGCCCCCTCTACTCACCTCCACTTGCCTGCATATATTTCTATTTG 2*01 TCTTTGCTTTTCAGCAGTTTTAATAAGATT SEQ ID NO: 265 IGHV(III)-2- GGGTTACTTTCCATGAGTACAAATAAATTAACAATCTCAAGCAACACCCTTTTAAGTGCAGTCTGCCTTACAATGACCAATCTGAAAG 1*01 CCAAGGACAAGGTCATGTATTACTGTGAGTGA SEQ ID NO: 266 IGHV(III)-25- GCAAGCTCCAGGACCAGGGTTGATGTGGGCAGCAACAGGGAGAAATTGAAGAGGAAGCTCTCAGTGGTGCCCTCCATGAATACAA 1*01 AGAATCTTCACAGTCCCCAGGACACCCTTACGTGC SEQ ID NO: 267 IGHV(III)-25- AGAGGAGCTCTCAGTGGTGCCCTCCATGAATACAAAGAATCTTCACAGTCCCCAGGACACCCTTACGTGCATGGTCTCACTGATAT 1*02 CTTTACTTCCTTTATCACTTTTGTTTGTAAAT SEQ ID NO: 268 IGHV(III)-25- GGGTTACTCTCCATGAGTACAGATAAATCAACATTCCCAAGTGACACCCTTTCAQAGTGCAGTCTACCTTACAAGGACCAACCTGAAA 1*01_IGHV(III)- GCCAAGGGCAAGGCCGTATATTACAGTGAGGGA 26-1*02 SEQ ID NO: 269 IGHV(III)-38- AATGGGACTCGCCTTCAGTACAAAGAAGATTAACAGTCCTCAGAGACACTGTTCAGAAGATTCTCTTTTAAGATAATAAAACTGAGA 1*01 GCCCAAGACAAGTCTGTGTATTACTGTGAGGGA SEQ ID NO: 270 IGHV(III)-38- AATGGGACTCGCCTTCAGTACAAAGAAGATTAACAGTCCTCAGAGACACTGTTCAGAAGATTCTCTTTTAAGATAATAAAACTGAGA 1*02 GCCCAAGACAAGTCTGTGTATTACTGTGAGGGA SEQ ID NO: 271 IGHV(III)-38- AGTGGGACTCTCCTTCAGTACAAAGAAGATTAACAGTCCTCAGAGACACTGTTCAGAAGATTCTCTTTAAGATAATTAAACCAAGA 1D*01 GCCCAGGACAAGTCTGTGTATTACTGTGAGGGA SEQ ID NO: 272 IGHV(III)- TTTAGGAAGAATGCCCCCTCAACTCATCTCCACTTGTCTGCATGTATTTCTATTTGTCTTGGACGTTCCCAACAGCCTCNCGAACACTC 44*01 ACCTCACCCTACAATGCTGCTCGAGGGGGTC SEQ ID NO: 273 IGHV(III)- ATTTTCCTCTTGCTTATAAGGTTTTAACCAGAAGAATGCTGTCATCATCTTTCCTGTTCTTTTAGAAGGAATGCCCCCTCAACTCATCTC 44D*01 CACTTGTCTGCATGTATTTCTATTTGTCTT SEQ ID NO: 274 IGHV(III)-5- GATTTATCATCTCAAGAGACAATGTCAAGAAGATGCTGTTTCTGCAAATGGGCAATCTGCAAACCAAGGACACGTCACTACATTACT 1*01 GTGCAAGAGAAG SEQ ID NO: 275 IGHV(III)-51- CAATGCAGACTATGTTAGGGGCAGACTCACCACTTCCAGAGACAACACCAAGTACATGCTGTACATGCAAATGAACAGCCTGAGAA 1*01 CCCAGAACATGGCAGCATTTAACTGTGCAGGAAA SEQ ID NO: 276 IGHV(III)-5- GGTGCTCTGCTCCAGCACAAAGAAGATTCACAGTTCCTGGGGACAACACTTAACATCACAATCTCCCTTAAAATTATCTACTGGAAA 2*01 GCTGAGGAGTAGGCAGTGTATTACTGTGAGAGA SEQ ID NO: 277 IGHV(III)-67- GATTTATTGTCTCCAGAGACAATGTCAAGAATATGCTATATCTGCAATGGGCGATCTGTAAACCAAGAACACATCAGTATATCACT 2*01 GTGCAAGAGGAG SEQ ID NO: 278 IGHV(III)-67- AGCATAATGAAGATTCACAATTCCCAGGGACACCAATTACCAGCACAGTCTCCCTTAAAATAATCTACTTGGAAGCTGAGGGGGCTC 3*01 TCACAGGGGTAGGCAGTGTATTACTGTGAGAGA SEQ ID NO: 279 IGHV(III)-67- AGGTTTACTCTTCATGAGTACAAATAAATTAACTGGTCCAGCGACACCCTTTCACGTGCACTCTACCTTACAATGACTAACCTGAAAG 4*-1 CCAAGGACAAGGTTGTGTAATACTGTGAGCTT SEQ ID NO: 280 IGHV(III)-76- TGGTACCCTCCATCAATACAAAGAAAAATCATAATCCTCAGGGACACCCTTGTCAGCACAGTCTCCCTCAAAATGACCACCTGAGA 1*01 GCCGAGGAGAAGGCCATGTATTACTGTGAGAGA SEQ ID NO: 281 IGHV(III)- GGGTTACTCTCCATGAGTACAAGTAAATTAACAGTCCCAAGCAACACCCTTTCAAGTGCAGTCTACCTTAAAATGACCAATGTGAAA 82*01 GCCAAGGACAAGACCTTGTATTACTGTGAGTGA SEQ ID NO: 282 IGHV(IV)-44- CTAAGCCCCAACCTTCAGGGCAGAGCTAGCATCTCCAGAAACACATAGTAAAAAACAAGAAAACTTACAGCTGAGAAGTGTGATGG 1*01 CTGGGGATGCAGGCGTGTATTACTGTGCTCAAGG SEQ ID NO: 283 IGHV1/OR15- AACTATGCACAGAAGTTTCAGGGCAGAGTCACCATGACCAGGGACACGTCCATCAGCACAGCCTACACGGAGCTGAGCAGCCTGA 1*01 GATCTGAGGACACGGCCACGTATTACTGTGCGAGA SEQ ID NO: 284 IGHV1/OR15- CTATGCACAGAAGTTTCAGGGCAGAGTCACCATGACCAGGGACACGTCCATCAGCACAGCCTGCACGGAGCTGAGCAGCCTGAGA 1*02 TCTGAGGACACGGCCACGTATTACTGTGCGAGAGA SEQ ID NO: 285 IGHV1/OR15- CTATGCACAGAAGTTTCAGGGCAGAGTCACCATGACCAGGGACACGTCCATCAGCACAGCCTACACGGAGCTGAGCAGCCTGAGA 1*03 TCTGAGGACACAGCCACGTATTACTGTGCGAGAGA SEQ ID NO: 286 IGHV1/OR15- CTATGCACAGAAGTTTCAGGGCAGAGTCACCATGACCAGGGACACGTCCATCAGCACAGCCTACATGGAGCTGAGCAGCCTGAGAT 1*04 CTGAGGACACGGCCACGTATTACTGTGCGAGAGA SEQ ID NO: 287 IGHV1/OR15- AACTACCCACAGAAGCTCCAGGGCAGAGTCACCATGACCAGAGACACATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGA 2*01 GATCTGACGACATGGCCGTGTATTACTGTGCGAGA SEQ ID NO: 288 IGHV1/OR15- CTACCCACAGAAGCTCCAGGGCAGAGTCACCATGACCAGAGACACATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGA 2*02_IGHV1/ TCTGACGACATGGCCGTGTATTACTGTGCGAGAGA OR15-2*03 SEQ ID NO: 289 IGHV1/OR15- AAATATTCACAGAAGCTCCAGGGCAGAGTCACCATTACCAGGGACACATCTTCGAGCACAGCCTACATGCAGCTGAGCAGCCTGAG 3*01 ATCTGAGGACACGGCCGTGTATTACTGTGCGAGA SEQ ID NO: 290 IGHV1/OR15- ATATTCACAGAAGCTCCAGGGCAGAGTCACCATTACCAGGGACACATCTGCGAGCACAGCCTACATGCAGCTGAGCAGCCTGAGAT 3*02 CTGAGGACACGGCCGTGTATTACTGTGCGAGAGA SEQ ID NO: 291 IGHV1/OR15- AAGTATTCACAGAAGCTCCAGGGCAGAGTCACCATTACCAGGGACACATCTGCGAGCACAGCCTACATGCAGCTGAGCAGCCTGAG 3*03 ATCTGAGGACACGGCCGTGTATTACTGTGCGAGA SEQ ID NO: 292 IGHV1/OR15- CGTTTCTCTGGCTCCAGGTCTGGCAACACGGCCTCCCTGACAATCTCTGGGCTCCAGGGCTGAGGACGAGGGAGATTATTACTGCAGT 4*01 TCATATACAGCCACTCCTCATATTCCTGTGATT SEQ ID NO: 293 IGHV1/OR15- AGCTATGCACAAAAGTTCCAGGCCAGAGTCACCATAACCAGGGACACATCCATGAGCACAGCCTACATGGAGCTAAGCAGTCTGAG 5*02 ATCTGAGGACACGGCCATGTATTACTGTGTGAGA SEQ ID NO: 294 IGHV1/OR15- TATATGCACAGAATTCCAGGGCAGAGTCACCACGACCTGGGACACGTCTACAGACACAGCCTACATGGAGCTGAGCAGCCTGAGAT 6*01 CTGAGGACACAGCCGTATATTAATGTGCAAGACA SEQ ID NO: 295 IGHV1/OR15- CTATGCACAGAAGTTCCAGGGCAGAGTCACCATAACCAGGGACACATCCATGGGCACAGCCTACATGGAGCTAAGCAGCCTGAGA 9*01 TCTGAGGACACGGCCATGTATTACTGTGTGAGAGA SEQ ID NO: 296 IGHV1/OR16- CTATGCACAGAAGTTTCAGGGCAGAGTCACCATGACCAGGGACATGTCCACGAGCACAGCCTACATGGAGCTGAGCAGTCAGAGA 2*01 TCTGAGGACATAGATGTGTACTACTGTGCGAGACA SEQ ID NO: 297 IGHV1/OR21- CTATGCACAGAAGTTCCAGGCCAGAGTCACCATAACCAGGGACACATCCATGAGCACAGCCTACATGGAGCTAAGCAGTCTGAGAT 1*01 CTGAGGACACGGCCATGTATTACTGTGTGAGAGA SEQ ID NO: 298 IGHV1-12*01 GTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAACCTCCCTGGCCATCAGTGGGCTCCGGTCCGAGGTAGAGGCTGATTAT TACTGTGCAGCATGGGATGACAGCCTGAGTGGT SEQ ID NO: 299 IGHV1-12*02 GTGAAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCTGGATACACCTTCACCTACTGCTACTTGCACTGGGTATGACA GGCCCCTGGACAAGGGCTTGAATGGACAGGATTT SEQ ID NO: 300 IGHV1-14*01 CTATGCACAGAAGTTTCAGGGCAGAGTCACCATGACCAGGGACACGTCCACGAGCACAGCCTACATGGAGCTGAGCAGTCAGAGA TCTGAGGACATAGATGTGTACTACTGTGCGAGACA SEQ ID NO: 301 IGHV1-17*02 CTACGCACAGAAGTTCCGGGGCAGAGTCACCATTACCAGTGACAGGTCCGTGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGA TCTGAAGACATGGTCGTGTATTCCTGTGTGAGAGA SEQ ID NO: 302 IGHV1-18*01 CACTGCACTGAACCTCCGGGGCAGAGTCTCCATGACCACAGACACATCCACAAACACAGTCTACATGGAGGTGAAGAGCCTAAGAT CTGACGACACGGCCATATATTTCTGTGCGCGAGA SEQ ID NO: 303 IGHV1-18*03 CTATGCACAGAAGCTCCAGGGCAGAGTCACCATGACCACAGACACATCCACGAGCACAGCCTACATGGAGCTGAGGAGCCTGAGA TCTGACGACATGGCCGTGTATTACTGTGCGAGAGA SEQ ID NO: 304 IGHV1-18*04 CTATGCACAGAAGCTCCAGGGCAGAGTCACCATGACCACAGACACATCCACGAGCACAGCCTACATGGAGCTGAGGAGCCTGAGA TCTGACGACACGGCCGTGTATTACTGTGCGAGAGA SEQ ID NO: 305 IGHV1-2*01 CCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCACTGGGCTCCAGGCTGACGATGAGGCAGATTATTAC TGCCAGTCCTATGACAGGGGTCTGAGTGGTCTC SEQ ID NO: 306 IGHV1-2*02 AACTATGCACAGAAGTTTCAGGGCAGGGTCACCACGACCAGGGACACGTCCATCAGCACAGCCTACATGGAGCTGAGCAGGCTGA GATCTGACGACACGGCCGTGTATTACTGTGCGAGA SEQ ID NO: 307 IGHV1-2*03 CTATGCACAGAAGTTTCAGGGCAGGGTCACCGTGACCAGGGACACGTCCATCAACACAGTCTACATGGAGCTGAGCAGACTGAGA TCTGACGACACGGCCGTGTATTACTGTGCGAGAGA SEQ ID NO: 308 IGHV1-2*04 CTATGCACAGAAGTTTCAGGGCTGGGTCACCATGACCAGGGACACGTCCATCAGCACAGCCTACATGGAGCTGAGCAGGCTGAGA TCTGACGACACGGCCGTGTATTACTGTGCGAGAGA SEQ ID NO: 309 IGHV1-2*05 ATCCCTGAGCGATTCTCTGGCTCCAGCTCAGGGACAACAGTCACGTTGACCATCAGTGGAGTCCAGGCAGAAGACGAGGTTGACTA TTACTGTCAATCAGCAGACAGCAGTGGTACTCCG SEQ ID NO: 310 IGHV1-24*01 GTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCGAGGACACATCTACAGACACAGCCTACATGGAGCCGGTCAGCCTGAGA TCTGACGACACGGCCGTCTATTACTGTGCAACAGA SEQ ID NO: 311 IGHV1-3*01 AAGTATTCACAGAAGTTTCAGGGGAGAGTCACCATTACCAGGGACACATCGGCGAACACAGCCTACATGGAGCTGAGTAGCCTAA GATCTGAAGACACGGCTGTGTATTACTGTGCGAGA SEQ ID NO: 312 IGHV1-3*02 ATATTCACAGGAGTTCCAGGGCAGAGTCACCATTACCAGGGACACATCCGCGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGAT CTGAGGACATGGCTGTGTATTACTGTGCGAGAGA SEQ ID NO: 313 IGHV1-38- CGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCGGGCACAGATTTTACACTGAAGATCAGCAGAGTGGAGCCTGAGGACATTGGG 4*01 GTTTATTACTGTATGCAGTCTCTCCAAACTCCTCA SEQ ID NO: 314 IGHV1-45*01 CTACGCAGAAATTCCAGGACAGAGTCACCATTACTAGGGACAGGTCTATGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGAT CTGAGGACACAGCCATGTATTACTGTGCAAGANA SEQ ID NO: 315 IGHV1-45*02 CCAACTACGCACAGAAATTCCAGGACAGAGTCACCATTACCAGGGACAGGTCTATGAGCACAGCCTACATGGAGCTGAGCAGCCTG AGATCTGAGGACACAGCCATGTATTACTGTGCAA SEQ ID NO: 316 IGHV1-46*01 GCTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAGGGACACGTTCCACGAGCACAGTCTACATGGAGCTGAGCAGCCTGAG ATCTGAGGACACGGCCGTGTATTACTGTGCGAGAG SEQ ID NO: 317 IGHV1-46*02 ATCCCTGAGAGATTCTCTGGCTCCAGCTCAGGGACAATGGCCACCTTGACCATTAGTGGGGCCCAGGTGGAGGATGAAGCTGACTA CTACTGTTACTCAACAGACACTAATGATAATCGG SEQ ID NO: 318 IGHV1-46*03 AAGTTCGCACAGAAATTCCAGGGCAGGGTCACCATTACGAGGGACACGTCCACGAGCACAGTCTACATGAAGCTGAGCAGCTTAA GATCTGAGGACACGGCCGTGTATTACTGTGCGACA SEQ ID NO: 319 IGHV1-58*01 CTACGCACAGAAGTTCCAGGAAAGAGTCACCATTACCAGGGACATGTCCACAAGTACAGCCTACATGGAGCTGAGCAGCCTGAGAT CCGAGGACACGGCCGTGTATTACTGTGCGGCAGA SEQ ID NO: 320 IGHV1-58*02 CTACGCACAGAAGTTCCAGGAAAGAGTCACCATTACCAGGGACATGTCCACAAGCACAGCCTACATGGAGCTGAGCAGCCTGAGAT CCGAGGACACGGCCGTGTATTACTGTGCGGCAGA SEQ ID NO: 321 IGHV1- AGCTACGCAGAGAAGTTCCAGGGCAGAGTCACCATGACCAGGGACACATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGA 67*01_IGHV1- GATCTGAAGACACGGCCATGTATTACTGTGGGAGA 67*02 SEQ ID NO: 322 IGHV1-68*01 CTATGCAAAGAAGTTCCAGGGCAGAGTCACCATTACCAGGGACATGTCCCTGAGGACAGCCTACATAGAGCTGAGCAGCCTGAGAT CTGAGGACTCGGCTGTGTATTACTGGGCAAGATA SEQ ID NO: 323 IGHV1-69*01 ATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGCCTGGAGCCTGAAGATTTTGCAGTTTAT TACTGTCAGCACCGGAGCAACTGGCTAATCGCC SEQ ID NO: 324 IGHV1- TCCGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACACTGAAAATCAGTAGAGTGGAGGCTGAGGATGTTG 69*02_IGLV3- GGGTTTATTATTGCATGCAAGCTCTACAAAGGGGA 2*02 SEQ ID NO: 325 IGHV1-69*04 AATACCGCACAGAGGTTCGAGGACAGAGTCACGATTACCGCGGACACATCGACGAGCACAGTCTTCATGGAACTGAGCAGCCTGA GATCTGAAGACACGGCCGTGTATTACTGTGCGAGA SEQ ID NO: 326 IGHV1-69*05 AGACTACGCACAGAAATTCCAGGGCAGAGTCACGATTGTCACGGACGAATCGACGAGCACATCCTACATGGAAGTGAAGAGCCTG AGATCTGAAGACACGGCCGTGTATTATTGTGCGAG SEQ ID NO: 327 IGHV1-69*06 ACTACGCACAGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACAAATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAG ATCTGAGGACACGGCCGTGTATTACTGTGCGAGAG SEQ ID NO: 328 IGHV1-69*07 GACTACGCACAGAAGTTTCAGGCCAGAGTCACAATAAGCGCGCACGAATTCACGCCCATAGTTTATATGGAGTTGAGAAGCCTGAG ATCCGACCAGCACGCCACATATTACTGTGCGACA SEQ ID NO: 329 IGHV1-69*08 AGACTACGCACAGAACTTCCAGGATAGAGTCAACATTAATGCGGACCAATCTACGAACACAGTCTACATGGAACTGAGCAGGCTGA CATCTGACGACACGGCCGTCTATTACTGTGCGAG SEQ ID NO: 330 IGHV1-69*09 CTCCGCTCAGAAGTTCCAAGACCGAGTCACCATTAGTGTCGACGAGTCCGCGGGCACAGTATACATGGACCTGGACAGCCTGACCT CTGAAGACACGGCCATGTATTACTGTGCGAAAGA SEQ ID NO: 331 IGHV1-69*10 AACTACGCACCGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACAAAACCACTAGTACTGCTTACATGGAGCTGAGCAGCCTGAG ATCTGAGGACACGCTCGTGTATTACTGTGCGAGA SEQ ID NO: 332 IGHV1- CTACGCACAGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACGAATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGA 69*11_IGHV1- TCTGAGGACACGGCCGTGTATTACTGTGCGAGAGA 69*12_IGHV1- 69D*01 SEQ ID NO: 333 IGHV1-69*13 ACTACGCACAGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACGAATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAG ATCTGAGGACACGGCCGTGTATTACTGTGCGAGAG SEQ ID NO: 334 IGHV1-69*14 CTACGCACAGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACAAATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGA TCTGAGGACACGGCCGTGTATTACTGTGCGAGAGA SEQ ID NO: 335 IGHV1-69- TGCTCGCACAGAAATTCCGGGGCAGAATCTCCATAACCGCGGACACGTCCACAGACACAACTTACATGGCGCTGAGCAGCCTGACC 2*01 TCTGATGACACGGCCGTCTATTACTGTTCAACAG SEQ ID NO: 336 IGHV1-8*01 GGCTATGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAGGAACACTCCATAAGCACAGCCTACATGGAGCTGAGCAGCCTGA GATCTGAGGACACGGCCGTGTATTACTGTGCGAGA SEQ ID NO: 337 IGHV1-8*02 CTATGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAGGAACACCTCCATAAGCACAGCCTACATGGAGCTGAGCAGCCTGAGAT CTGAGGACACGGCCGTGTATTACTGTGCGAGAGG SEQ ID NO: 338 IGHV2/OR16- ACAGCACGTCTCTGAAGAACAGGCTCATCATCTCCAAGGACACCTCCAAAAGCCAGGTGGTCCTTACCATGACCAACATGGACCCTG 5*01 TGGACACAGCCACGTATTACTGTGCATGGAGAG SEQ ID NO: 339 IGHV2-10*01 ACAGCCCATCTCTGAAGAGTAGGCTCATTATCTCCAAGGACACCTCCAAGAATGAAGTGGTTCTAACAGTGATCAACATGGACATTG TGGACACAGCCACACATTACTGTGCAAGGAGAC SEQ ID NO: 340 IGHV2-25*01 TACAGGACATCTCTGAAGAGCAGGCTCTCCATCTCCAAGGACACCTCCAAAAGCCTGGTGGCCTTACCATGACCAACATGGACCCT GTGGACACAGCCACGTATTATTGTGCACGGATA SEQ ID NO: 341 IGHV2- TCCGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACACTGAAAATCAGTAGAGTGGAGGCTGAGGATGTTG 5*01_IGHV3- GGATTTATTACTGCATGCAAGCTCTACAAACCCCA 30*13_IGHV4- 30-4*01 SEQ ID NO: 342 IGHV2- ACAGCCCATCTCTGAAGAGCAGGCTCACCATCACCAAGGACACCTCCAAAAACCAGGTGGTCCTTACAATGACCAACATGGACCCTG 5*02_IGHV2- TGGACACAGCCACATATTACTGTGCACACAGAC 5*03 SEQ ID NO: 343 IGHV2- ACGGCCCATCTCTGAAGAGCAGGCTCACCATCACCAAGGACACCTCCAAAAACCAGGTGGTCCTTACAATGACCAACATGGACCT 5*05_IGHV2- GTGGACAGAGCCACATATTACTGTGCACACAGAT 5*09 SEQ ID NO: 344 IGHV2-5*06 TACGGCCCATCTCTGAAGAGCAGGCTCACCATCACCAAGGACACCTCCAAAAACCAGGTGGTCCTTACAATGACCAACATGGACCCT GTGGACACAGCCACATATTACTGTGCACACAGA SEQ ID NO: 345 IGHV2-5*07 AGGCGCTACAGACCCTCTCTGAAGACCAGACTCACCATTCACCCAGGACATGTCCAGGAACCAGGTGGTCCTTAGACTGACCAACTT GGACCCACTGGACACAGGCACATATTTTTGTGCA SEQ ID NO: 346 IGHV2-5*10 AGCGCTACAGCCCATCTCTGAAGAGCAGGCTCACCATCACCAAGGACACCTCCAAAAACCAGGTGGTCCTTACAATGACCAACGTG GACCCTGTGGACACAGCCACATATTACTGTGCAC SEQ ID NO: 347 IGHV2-70*01 CTACAGCACATCTCTGAAGACCAGGCTCACCATCTCCAAGGACACCTCCAAAAACCAGGTGGTCCTTACAATGACCAACATGGACCC TGTGGACACAGCCACGTATTACTGTGCACGGAT SEQ ID NO: 348 IGHV2-70*04 TACAGCACATCTCTGAAGACCAGGCTCACCATCTCCAAGGACACCTCCAAAAACCAGGTGGTCCTTACAATGACCAACATGGACCCT GTGGACACAGCCACGTATTACTGTGCACGGATA SEQ ID NO: 349 IGHV2-70*06 TGATAAATTCTACAGCACATCCCTGAAGACCAGGCTCACCATCTCCAAGGACACCTCCAAAAACCAGGTGGTCCTTACAATGACCAA CATGGACCCTGTGGACACGGCCGTGTATTACTG SEQ ID NO: 350 IGHV2- ACAGCACATCTCTGAAGACCAGGCTCACCATCTCCAAGGACACCTCCAAAAACCAGGTGGTCCTTACAATGACCAACATGGACCCTG 70*10_IGHV2- TGGACACAGCCACGTATTACTGTGCACGGATAC 70*11_IGHV2- 70D*04_IGHV2- 70D*14 SEQ ID NO: 351 IGHV2-70*12 ACAGCACATCTCTGAAGACCAGGCTCACCATCTCCAAGGACACCTCCAAAAACCAGGTGGTCCTTACAATGACCAACATGGACCCTG TGGACACAGCCACATATTACTGTGCACACAGAC SEQ ID NO: 352 IGHV2-70*13 ACAGCACATCTCTGAAGACCAGGCTCACCATCTCCAAGGACACCTCCAAAAACCAGGTGGTCCTTACAATGACCAACATGGACCCTG TGGACACAGCCACGTATTATTGTGCACGGATAC SEQ ID NO: 353 IGHV3/OR15- GAATATGCTGCGTCTGTGAAAGGCAGACTTACCATCTCAAGAGAGGATTCAAAGAACACGATGTATCTGCAAATGAGCAACCTGAA 7*01 AACCGAGGACTTGGCCGTGTATTACTGTGCTAGA SEQ ID NO: 354 IGHV3/OR15- GAATATGCTGCGTCTGTGAAAGGCAGACTTACCATCTCAAGAGAGGATTCAAAGAACACGCTGTATCTGCAAATGAGCAGCCTGAA 7*02_IGHV3/ AACCGAGGACTTGGCCGTGTATTACTGTGCTAGA OR15-7*03 SEQ ID NO: 355 IGHV3/OR15- TATGCTGCGTCTGTGAAAGGCCAGACTTACCATCTCAAGAGAGGATTCAAAGAACACGCTGTATCTCAAATGAGACAGCCTGAAAA 7*04 CCGAGGACTTGGCCGTGTATTACTGTGCTAGAGA SEQ ID NO: 356 IGHV3/OR15- ATATGCTGCGTCTGTGAAAGGCAGACTTACCATCTCAAGAGAGGATTCAAAGAACACGCTGTATCTGCAAATGAGCAACCTGAAAA 7*05 CCGAGGACTTGGCCGTGTATTACTGTGCTAGAGA SEQ ID NO: 357 IGHVE/OR16- CTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATGCCAAGAACTCCTTGTATCTTCAAATGAACAGCCTGAGAGC 10*01_IGHV3/ CGAGGACATGGCTGTGTATTACTGTGCAAGAGA OR16- 10*03_IGHV3/ OR16- 11*01 SEQ ID NO: 358 IGHV3/OR16- TACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATGCCAAGAACTCCTTGTATCTTCAAATGAACAGCCTGAGA 10*02 GCCGAGGACATGGCTGTGTATTACTGTGCAAGA SEQ ID NO: 359 IGHV3/OR16- AACTACGCAGACTCTGTGAAGGGCAGATTCACCATCTCCACAGACAACTCAAAGAACACGCTCTACCTGCAAATGAACAGCCTGAG 12*01 AGTGGAGGACACGGCCGTGTATTACTGTGCAAGA SEQ ID NO: 360 IGHV3/OR16- AGCTACGCAGACTCCATGAAGGGCCAATTCACCATCTCCAGAGACAATGCTAAGAACACGCTGTATCTGCAAATGAACAGTCTGAG 13*01 AGCTGAGGACATGGCTGTGTATTACTGTACTAGA SEQ ID NO: 361 IGHV3/OR16- AGCTACGCAGACTCCTTGAAGGGCCAATTCACCATCTCCAGAGACAATGCTAAGAACACGCTGTATCTGCAAATGAACAGTCTGAG 14*01 AGCTGAGGACTATGGCTGTGTATTACTGTACTAGA SEQ ID NO: 362 IGHV3/OR16- CTATGTGGACTCCGTGAAGGGCCAATTTTCCATCTCCAGAGACAATTCCAGCAAGTCCCTGTATCTGCAAAAGAACAGACAGAGAG 15*01 CCAAGGACATGGCCGTGTATTACTGTGTGAGAAA SEQ ID NO: 363 IGHV3/OR16- CACTATGTGGACTCCGTGAAGGGCCAATTTACCATCTCAGAGACAATTCCAGCAAGTCCCTGTATCTGCAAAAGAACAGACAGAG 15*02 AGCCAAAGACATGGCCGTGTATTACTGTGTGAGA SEQ ID NO: 364 IGHV3/OR16- CACTATGTGGACTCCGTGAAGGGCCAATTTACCATCTCCAGAGACAATTCCAGCAAGTCCCTGTATCTGCAAAAGAACAGACAGAG 16*01 AGCCAAGGACATGGCCGTGTATTACTGTGTGAGA SEQ ID NO: 365 IGHV3/OR16- CTACGCTGCACCTGTGAAAGGCAGATTCACCATCTCAAGAGTTGATTCAAAAAACACGCTGTATCTGCAAATGAACAGCCTGAAAAC 7*01 CGAGGACACGGCCGTGTATTACTGTACCACAGA SEQ ID NO: 366 IGHV3/OR16- GACTACGCTGCACCTGTGAAAGGCAGATTCACCATCTCAAGAGTTGATTCAAAAAACACGCTGTATCTGCAAATGAACAGCCTGAA 7*02 AACCGAGGACACGGCCGTGTATTACTGTACCACA SEQ ID NO: 367 IGHV3/OR16- AACTACGCAGACTCTGTGAAGGGCCGATTCACCATCTCCAGGGACAACGCCAATAACTCACCGTATCTGCAAATGAACAGCCTGAGA 8*01 AGCTGAGGACACGGCTGTGTATTACTGTGTGAAA SEQ ID NO: 368 IGHV3/OR16- CTACGCAGACTCTGTGAAGGGCCGATTCACCATCTCCAGGGACAACGCCAATAACTCACCGTATCTGCAAATGAACAGCTTGAGAG 8*02 CTGAGGACACGGCTGTGTATTACTGTGTGAAACA SEQ ID NO: 369 IGHV3/OR16- GGGGTCCCATCAAGGTTCACCGCCAGTGGATCTGGGACAGAATTCACTCTCAATATCAGCAGCCTGCACCCTGACGATTTTGCAACT 9*01 TATTACTGCCAGCAATATGAGCCTTATACCCCC SEQ ID NO: 370 IGHV3-11*01 GTATGGAGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACGCCCTGTATTTACAGATGAACAGCCTGAGAG CCGAGGACACGGCTGTCTATTACTGTGCGACAGA SEQ ID NO: 371 IGHV3-11*02 GGGATCCCTGATCGCTTCTCAGGCTCCAGCTCTGGGGCTGAGCTCTACCCTCACCATCTCGAGCCTCCAGTCTGAGGATGAGGCTGAC TATTACTGTCAGACCTGGGGCACTGACATTCAG SEQ ID NO: 372 IGHV3-11*03 AACTACGCAGACTCTGTGAAGGGCCGCTTCACCATCTCCAGAGACAACGCCAACAACTCACTGTTTCTGCAAATGAACAGCCTGAGA GCCGAGGACGCGGCCGTGTATGACTGTGCGAGA SEQ ID NO: 373 IGHV3-11*04 CCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGCCTCCAGTCTGAGGATGAGGCTGATTATTACT GTGCACCATGGGATGACAGCCTGAATGGTCCG SEQ ID NO: 374 IGHV3-11*05 CTACGCAGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGAGAG CCGAGGACACGGCCGTGTATTACTGTGCGAGAGA SEQ ID NO: 375 IGHV3-11*06 CTACGCAGTCTCTGTGAAGGGCCGATTCACCATCTCCAGAGACGACGCCGCTAACTCAGTGTATCTGCAAATGAACAGCCTGCGAGA CCGAGGACACGGCTGTGTATTTCTGTGCGAGAGA SEQ ID NO: 376 IGHV3-13*01 ACTATCCAGGCTCCGTGAAGGGCCGATTCACCATCTCCAGAGAAAATGCCAAGAACTCCTTGTATCTTCAAATGAACAGCCTGAGAG CCGGGGACACGGCTGTGTATTACTGTGCAAGAG SEQ ID NO: 377 IGHV3-13*02 CTATCCAGGCTCCGTGAAGGGGCGATTCACCATCTCCAGAGAAAATGCCAAGAACTCCTTGTATCTTCAAATGAACAGCCTGAGAGC CGGGGACACGGCTGTGTATTACTGTGCAAGAGA SEQ ID NO: 378 IGHV3-13*03 TACTATCCAGGCTCCGTGAAGGGCCAATTCACCATCTCCAGAGAAAATGCCAAGAACTCCTTGTATCTTCAAATGAACAGCCTGAGA GCCGGGGACACGGCTGTGTATTACTGTGCAAGA SEQ ID NO: 379 IGHV3-13*04 CTATCCAGGCTCCGTGAAGGGCCGATTCACATCTCCAGAGAAAATGCCAAGAACTCCTTGTATCTTCAAATGAACAGCCTGAGAGC CGGGGACACGGCTGTGTATTACTGTGCAAGAGA SEQ ID NO: 380 IGHV3-13*05 ACTATCCAGACTCCGTGAAGGGCCGATTCACTATCTCCAGAGAAAATGCCAAGAACTCCTTGTATCTGCAAATGAACAGCCTGAGAG TCGGGGACACGGCTGTATATTACTGTGCAAGAG SEQ ID NO: 381 IGHV3-15*01 GACTACGCTGCATCCGTGAAAGACAGATTCACCATCTCAAGAGATGATTCAAAAAATACGGTGTTTCTGCAACTGAACAGCCTGAAA ACCGAGGACACAGCCGTCTATTACTGTACCACA SEQ ID NO: 382 IGHV3-15*02 ACTACGCTGCACCCATTAAAGGCAGATTCACCATCTCAAGAGATGATTCAAGAAACACACTGTTTCTGCAAATGAACAGCCTGAAAA ACGAAGACACAGCCATGTATTTTTGTACCACAG SEQ ID NO: 383 IGHV3-15*03 CTACGCTGCACCTGTGAAAGGCAGATTCACCATCTCAAGAGTTGATTCAAAAAACACGCTGTATCTGCAAATGAACAGCCTGAAAAC CGAGGACACAGCCGTGTATTACTGTACCACAGA SEQ ID NO: 384 IGHV3- CTACGCTGCACCCGTGAAAGGCAGATTCACCATCTCAAGAGATGATTCAAAAAACACGCTGTATCTGCAAATGAACAGCCTGAAAA 15*04_IGHV3- CCGAGGACACAGCCGTGTATTACTGTACCACAGA 15*06 SEQ ID NO: 385 IGHV3-15*05 ATAGACTATGCTGCACCCGTGAAAGGCAGATTCATCATTTCAAGAGATGATTCAAAAAGTACGGTGTATTTACAAATGAACAGACTG AAAATTGAGGACACAGCCGTATATTATTGTGTC SEQ ID NO: 386 IGHV3-15*07 ACTACGCTGCACCCGTGGAAGGCAGATTCACCATCCTAAGAGATGATTCAAAGAACACGCTGTATTTAACAATGAACAGCCTGAAA ACCGAGGACACAGGCGTGTATTATTGTCTTTCAG SEQ ID NO: 387 IGHV3- CTACGCTGCACCTGTGAAAGGCAGATTCACCATCTCAAGAGATGATTCAAAAAACACGCTGTATCTGCAAATGATCAGCCTGAAAAC 15*08_IGHV3/ CGAGGACACGGCCGTGTATTACTGTACCACAGG OR16- 6*01_IGHV3/ OR16-6*02 SEQ ID NO: 388 IGHV3- CTATGTGGACTCCGTGAAGCGCCGATTCATCATCTCCAGAGACAATTCCAGGAACTCCCTGTATCTGCAAAAGAACAGACGGAGAG 16*01_IGHV3- CCGAGGACATGGCTGTGTATTACTGTGTGAGAAA 16*02 SEQ ID NO: 389 IGHV3-19*01 CTATGCAGACTCTGTGAAGGGCCGATTCATCATCTCCAGAGACAATTCCAGGAACTTCCTGTATCAGCAAATGAACAGCCTGAGGCC CGAGGACATGGCTGTGTATTACTGTGTGAGAAA SEQ ID NO: 390 IGHV3-20*01 TTATGCAGACTCTGTGCAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACTCCCTATATCTGCAAATGAACAGTCTGAGAGC CGAGGACACGGCCTTGTATTACTGTGCGAGAGA SEQ ID NO: 391 IGHVE-20*02 TTATGCAGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACTCCCTGTATCTGCAAATGAACAGTCTGAGAGC CGAGGACACGGCCTTGTATCACTGTGCGAGAGA SEQ ID NO: 392 IGHV3-21*01 ATTACGCAGACTCAGCGAAGGGGCGATTCACCATCTCCAGAGACAACGCCAAGAACTCAATGTATCTGCAAATGAACAGCCTGAGA GCCGAGGACACGGCTATGTATTACTGTGCGACCG SEQ ID NO: 393 IGHV3-21*02 TATACTATGCAGACTCACTGAGGGGCCGATTCACCATCTCCAGAGACAACGCCAGAAATTCACTGTCTCTGCAAATCAACGACCTGC GACCCGACGACACGGCTATATATTATTGTGCGA SEQ ID NO: 394 IGHV3-21*03 CTACGCAGACTCAGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGAGAG CCGAGGACACAGCTGTGTATTACTGTGCGAGAGA SEQ ID NO: 395 IGHV3-21*04 CTACGCAGACTCAGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGAGAG CCGAGGACACGGCCGTGTATTACTGTGCGAGAGA SEQ ID NO: 396 IGHV3-22*02 ATAGACCACGTCTGTGAAAGGCAGATTCACAATCTCAAGAGATGATTCCAAAAGCATCACCTATCTGCAAATGAAGAGCCTGAAAA CCGAGGACACGGCCGTGTATTACTGTTCCAGAGA SEQ ID NO: 397 IGHV3-23*01 ATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGA GAGCCGAGGACACGGCCGTATATTACTGTGCGAA SEQ ID NO: 398 IGHV3-23*02 CTACGGAGACTCCGTGAAGGGCCGGTTCACCATCTCAAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAG CCGAGGACACGGCCGTATATTACTGTGCGAAAGA SEQ ID NO: 399 IGHV3- ATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGCCTGGAGCCTGAAGATTTTGCAGTTTAT 23*03_IGKV1/ TACTGTCAGCAGCGTAGCAACTGGCTAATCGCC OR-4*01 SEQ ID NO: 400 IGHV3-23*04 ACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGA GCCGAGGACACGGCCGTGTATTACTGTGCGAAAG SEQ ID NO: 401: IGHV3-23*05 TATTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCAAGAGACAATTCCAGGAACACACTGTTTGTGCAATTGAATAGCCTGAGA GTCGAGGACACGGCCATATATTATTGTGCGAAA SEQ ID NO: 402 IGHV3- CTACGCAGACTCCGTGAAGGGCCGGTTCACATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAG 23D*01_IHGV3- CCGAGGACACGGCCGTATATTACTGTGCGAAAGA 23D*02 SEQ ID NO: 403 IGHV3- CCTCATAGACTCCGGTAAGGACCGATTCAATACCTCCAGAGATAACGCCAAGAACACACTTCATCTGCAAATGAACAGCCTGAAAAC 25*01_IGHV3- CGAGGACACGGCCCTCTATTAGTGTACCAGAGA 25*02_IGHV3- 25*05 SEQ ID NO: 404 IGHV3-25*03 CCTCATAGACTCCGGTAAGGACCGATTCAATACCTCCAGAGATAACGCCAAGAACACACTTCATCTGCAAATGAACAGCCTGAAAAC CGAGGACACGGCCCTGTATTAGTGTACCAGAGA SEQ ID NO: 405 IGHV3-25*04 ACTGGTATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC AGTTTATTACTGTCAGCAGTATAATAACTGGCAG SEQ ID NO: 406 IGHV3- ATGCAGACTCTGTGAAGGGCAGATTCTCCATCTCCAAAGACAATGCTAAGAACTCTCTGTATCTGCAAATGAACAGTCAGAGAACTG 29*01_IGHV3- AGGACATGGCTGTGTATGGCTGTACATAAGGTT 30-42*01 SEQ ID NO: 407 IGHV3-30*01 CTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAGGAACACACTGTATCTGGCAATGAACAGCCTGAGAG TTGAGGACACGGCTGTGTATTACTGTGTGAGAGA SEQ ID NO: 408 IGHV3-30*02 CTACGCAGAGTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACCCTGTATCTTCAACTGAACAGCCTGAGAGC TGAGGACACGGCTGTGTATTATTGTGCGAAAGA SEQ ID NO: 409 IGHV3-30*03 CTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAG CTGAGGACACGGCTGTGTATTACTGTGCGAGAGA SEQ ID NO: 410 IGHV3- TCCGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACACTGAAAAATCAGTAGAGTGGAGGCTGAGGATGTTG 30*04_IGHV3- GGGTTTATTACTGCATGCAAGCTCTACAAACCCCA 30*07 SEQ ID NO: 411 IGHV3-30*08 CCTGAGCGATTCTCTGGCTCCAACTCTGGCAACACAGCCACTCTGACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTAC TGTCAGGCGTGGGACAGCAGCACTGCCGATGTG SEQ ID NO: 412 IGHV3-30*09 ACACTATGCAGACTCCGTTCAGGGCCGATTCGGCGTCTCCAGAGACAATTCCAACTACACGGCGTACGTGCAACTGAACAGCCTGA GACCAGACGACACGGCTGTTTATTTTTGTGCGAG SEQ ID NO: 413 IGHV3-30*10 TCTACACAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACAGTGGATTTGCAGATGACTAACCTGAGC GATGACGACACGGCTGTGTACTTCTGTGCGAAAG SEQ ID NO: 414 IGHV3-30*12 CTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAG CCGAGGACACGGCTGTGTATTACTGTGCGAGAGA SEQ ID NO: 415 IGHV3-30*14 TTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACATTGTTCCTCCAAATGAACAGCCTGAGAGT AGAGGACACGGCTCTCTATTACTGTGCGAAAGA SEQ ID NO: 416 IGHV3-30*15 CTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAGCAGCCTGAGAG CTGAGGACACGGCTGTGTATTACTGTGCGAGAGA SEQ ID NO: 417 IGHV3-30*16 TTTACGCAGACTCCATGAAGGGCCGCTTCACCATCTCCAGAGAGAACTCCAAGAACACGCTGCATCTGCACATGAACAGCCTGAGA CCTGAGGACACGGCTGTCTATTACTGTGCGAGAG SEQ ID NO: 418 IGHVE-30*19 TTTTACTCAGACTCCATGAAGGGGCGGTGCACCATTTCCAGAGACAACTCCAAGCAGACAGTGTATTTGGAAATAGACACCCTGGA AACTGAAGACACGGCGGTATTCCTGTGTGAAA SEQ ID NO: 419 IGHV3-30- TTATGCATAATCTTTGAAGAGCAAATTCACCATCTCCAAAGAAAATGCCAAGAACTCACTGTATTTGCTAATGAACAGTCTGAGAGC 2*01_IGHV3- AGCGGGCACAGCTGTGTGTTACTGTATGTGAGG 30-52*01 SEQ ID NO: 420 IGHV3-30- ATGCAGACTCTGTGAAGGGCAGATTCTCCATCTCCAAAGACAATGCTAAGAACTCTCTGTATCTGCAAATGAACAGTCAGAGAGCTG 22*01 AGGACATGGACGTGTATGGCTGTACATAAGGTC SEQ ID NO: 421 IGHV3-30 CTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAG 3*01_IGHV3- CTGAGGACACGGCTGTGTATTACTGTGCGAGAGA 30- 3*03_IGHV3- 30*06_IGHV3- 30*11_IGHV3- 30*17 SEQ ID NO: 422 IGHV3-30- GGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAAATTTTGCAACT 3*02 TACTACTGTCAACAGAGTTACAGTACCCCTTGG SEQ ID NO: 423 IGHV3-30- TTATGCATAATCTTTGAAGAGCAAATTCACCATCTCCAAAGAAAATGCCAAGAACTCACTGTATTTGCTAATGAACAGTCTGAGAGC 33*01 AGAGGGCACAGCTGTGTGTTACTGTATGTGAGG SEQ ID NO: 424 IGHV3-30- CTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAG 5*01_IGHV3- CTGAGGACACGGCTGTGTATTACTGTGCGAAAGA 30- 5*02_IGHV3- 30*18_IGHV3- NL1*01 SEQ ID NO: 425 IGHV3-32*01 ATGCAGACTCTGTGAAGGGCAGATTCTCCATCTCCAAAGACAATGCTAAGAACTCTCTGTATCTGCAAATGAACACTCAGAGAGCTG AGGACGTGGCCGTGTATGGCTATACATAAGGTC SEQ ID NO: 426 IGHV3-33*01 CTATGCAGACTCCGTGAAGGGCCGATTCACCATCCCCAGAGGCAATTTCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGTG CCGAGGACGCGGCTGTGTATTACTGTGCGAGAGA SEQ ID NO: 427 IGHV3-33*02 CTATGCAGACTCCGCGAAGGGCCGATTCACCATCTCCAGAGACAATTCCACGAACACGCTGTTTCTGCAAATGAACAGCCTGAGAG CCGAGGACACGGCTGTGTATTACTGTGCGAGAGA SEQ ID NO: 428 IGHV3-33*03 ATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTA TTACTGTCAACACTATCGTAGTTCACCTCGGAAG SEQ ID NO: 429 IGHV3-33*04 CTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAG CCGAGGACACGGCTGTGTATTACTGTGCGAGAGA SEQ ID NO: 430 IGHV3-33*05 TTACGCAGACTCCGTGAAGGGCCGATTCATCGTCTCCAGAGACAATTCCAGGGACACGGTGTTTCTGCAGATGAGCAGCCTGAGAC TCGAGGACACGGCTGTCTATTACTGTGCGACAGA SEQ ID NO: 431 IGHV3-33*06 CTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAG CCGAGGACACGGCTGTGTATTACTGTGCGAAAGA SEQ ID NO: 432 IGHV3-33 TTATGCCCAATCTGTGAAGAGCAAATTCACCATCTCCAAAGAAAATGCCAAGAACTCACTGTATTTGCAAATGAACAGTCTGAGAGC 2*01 AGAGGGCACAGCTGTGTGTTACTGTATGTGAGG SEQ ID NO: 433 IGHV3-35*01 CACTATGCAGACTCTGTGAAGGGCCGATTCATCATCTCCAGAGACAATTCCAGGAACACCCTGTATCTGCAAACGAATAGCCTGAGG GCGAGGACACGGCTGTGTATTACTGTGTGAGA SEQ ID NO: 434 IGHV3- AGCTATGCAGACTCTGTGAAGGGTCGATTCACCCTCTCCAGAGATGATGCCAAGAAATCACTGTATCTGCAAATGAACAGCGTCAG 36*01_IGHV3- AGCCGAGGATAGGTCTGTGTATTACTGTGGTGGC 3- 36*02_IGHV3- 36*03 SEQ ID NO: 435 IGHV3-37*01 GGTAGTCTATACTATGCAGACACTGAAGGGTAGATTCACCATCTCTAGAGACAATGGCAAGAACATGCTGTTCTTGCAAATGAACA GTCTGAGAGATGAGGACTCGGTTGTGTTGAGAGA SEQ ID NO: 436 IGHV3-37*02 TGGTAGCCTATACTATGCAGACACTGAAGGGTAGATTCACATCTCTAGAGACAATGGCAAGAACATGCTGTACTTGCAAATGAAC AGTCTGAGAGATGAGGACTCGGCTGTGTGAGAGA SEQ ID NO: 437 IGHV3-38*01 ACGCAGACTCCAGGAAGGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAACCTGAGAGCT GAGGGCACGGCCGCGTATTACTGTGCCAGATATA SEQ ID NO: 438 IGHV3- ACGCAGACTCCAGGAAGGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAACCTGAGAGCT 38*02_IGHV3- GAGGGCACGGCCGTGTATTACTGTGCCAGATATA 3-38*03 SEQ ID NO: 439 IGHV3-380 CTACGCAGACTCCAGGAAGGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGCATCTTCAAATGAACAGCCTGAGAG 3*01 CTGAGGACACGGCTGTGTATTACTGTAAGAAAGA SEQ ID NO: 440 IGHV3-41*01 ATACTATGCAGACTCTGTGAAGGGCCGATTCACAATCTCCGAGACAATTCTAAGAGCATGCTCTATCTGCAAATGGACAGTCTGAAA GCTAAGGACACGGCCATGTATTACTGTACCAGA SEQ ID NO: 441 IGHV3- ATGCGCTGCATCTGTGAAAGGCAGGTTCACCATCTCAAGAGATGATTCAAAGAACACQACTGTATATGCAAATGAATACCCTGAAAA 42*02_IGHV3- CCAAGTACACGGCCATCTATTACTGTACTAGAGA 42D*01 SEQ ID NO: 442 IGHV3-42*03 ATGCGCTGCATCTGTGAAAGGCAGGTTCACCATCTCAAGAGATGATTCAAAGAACACACTGTATCTGCAAGTGAATACCCTGAAAA CCGAGTACACGGCCATCTATTACTGTACTAGAGA SEQ ID NO: 443 IGHV3-43*01 ATTATGCAGCCTCTGTGAAGGGTCGATTCACCATCTCCAGAGACAACTCCAAAAACTCCCTGTTTTTGCCAAATGAACAGTCTGAGAG TTGAAGATTCCGCCTTCTATTACTGTGGAAAAG SEQ ID NO: 444 IGHV3-43*02 TACTATGCAGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACAGCAAAAACTCCCTGTATCTGCAAATGAACAGTCTGAGA ACTGAGGACACCGCCTTGTATTACTGTGCAAAA SEQ ID NO: 445 IGHV3- ATGCAGACTCTGTGAAGGGTCGATTCACCATCTCCAGAGACAACAGCAAAAACTCCCTGTATCTGCAAATGAACAGTCTGAGAGCT 43D*01 GAGGACACCGCCTTGTATTACTGTGCAAAAGATA SEQ ID NO: 446 IGHV3-47*01 TACTATGCAGACTCCGTGATGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAAGTCCTTGTATCTTCATATGAACAGCCTGATA GCTGAGGACATGGCTGTGTATTATTGTGCAAGA SEQ ID NO: 447 IGHV3-47*02 TACTATGCAGACTCCGTGATGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAAGTCCTTGTATCTTCAAATGAACAGCCTGATA GCTGAGGACATGGCTGTGTATTATTGTGCAAGA SEQ ID NO: 448 IGHV3-48*01 TACTACGCAGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAATGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGAG AGCCGAGGACACGGCTGTGTATTACTGTGCGAGA SEQ ID NO: 449 IGHV3-48*02 TACTACGCAGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAATGCCAGGAGTCACTGTATCTGCAAATGACCAGCCTGAG AGTCGAGGACACGGCTGTATATCACTGTGCGAGG SEQ ID NO: 450 IGHV3-48*03 TACTACGCAGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAGTGCCAAGAATTCACTGTATCTGCACATGCACAGCCTGAGA GCCGAGGACACGGCTGTTTATTACTGTGCGAGA SEQ ID NO: 451 IGHV3-48*04 CTACGCAGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGAGAG CCGAGGACACGGCTGTGTATTACTGTGCGAGAGA SEQ ID NO: 452 IGHV3-49*01 ATACACCGCGTCTGTGAAAGGCAGATTCACCATCTCAAGAGATGGTTCCAAAAGCATCGCCTATCTGCAAATGAACAGCCTGAAAA CCGAGGACACAGCCGTGTATTACTGTACTAGAGA SEQ ID NO: 453 IGHV3- ATACGCCGCGTCTGTGAAAGGCAGATTCACCATCTCAAGAGATGATTCCAAAAGCATCGCCTATCTGCAAATGAACAGCCTGAAAA 49*02_IGHV3- CCGAGGACACAGCCGTGTATTACTGTACTAGAGA 49*03 SEQ ID NO: 454 IGHV3-49*04 AAATACGCCGCGTCTGTGAAAGGCAGATTCACCATCTCAAGAGATGATTACAAAAGCGTCGTCTATCTGCAAATGAACAGCCTGAG AAGCGAGGACACGCCGTATACTACTGTACTAGA SEQ ID NO: 455 IGHV3-49*05 GAATACGCCGCGTCTGTGAAAGGCAGATTCACCATCTCAAGAGATGATTCCAAAAGCATCGCCTATCTGCAAATGAACAGCCTGAA AACCGAGGACACAGCCGTGTATTACTGTACTAGA SEQ ID NO: 456 IGHV3-50*01 ATGCAGACTCTGTGAAGGTCAGATTCACCATCTCCAAAGACAATGCCAAGCACAGGTTGTATCTGCAAATGAACAGTCTGAGAGCT GAGAATATGGCTCTGTATTATTGAGTCAAAGGTA SEQ ID NO: 457 IGHV3-52*01 CTATGTAGACTCTGTGAAGGGCCGATTGACCATCTCCAGAGACAATGCCAAGAACTCCCTCTATCTGCAAGTGAACAGCCTGAGAG CTGAGGACATGACCGTGTATTACTGTGTGAGAGG SEQ ID NO: 458 IGHV3-52*03 TACTATGTAGACTCTGTGAAGGGCCGATTGACCATCTCCAGAGACAATGCCAAGAACTCCCTCTATCTGCAAGTGAACAGCCTGAGA GCTGAGGACATGACCGTGTATTACTGTGTGAGA SEQ ID NO: 459 IGHV3-53*01 CTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAG CCGAGGACACGGCCGTGTATTACTGTGCGAGAGA SEQ ID NO: 460 IGHV3-53*02 TACTATGCAGACTCTGTGAAGGGCGATTCACCATCTCCAGAGACAACAGCAAAAACTCCCTGTATCTGCAAATGAACAGTCTGAAA ACTGAGGACACCGCCTTGTATTACTGTGTGAAA SEQ ID NO: 461 IGHV3-53*03 CTACGCAGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGC CGAGGACACGGCCGTGTATTACTGTGCTAGGGA SEQ ID NO: 462 IGHV3-53*04 GTTTCTCATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCATCTCTGGGCTCCGGGCTGAGGACGAGGGTGATTAT TACTGCACCTCATATACAATCAATAGCGATTTT SEQ ID NO: 463 IGHV3-54*02 TTATGCACAATCTGTGAAGAGCAGATTCACCATCTCCAAAGAAAATGCCAAGAACTCACTCCGTTTGCAAATGAACAGTCTGAGAGC AGAGGGCACGGCCGTGTATTACTGTATGTGAGG SEQ ID NO: 464 IGHV3-54*04 TTATGCACAATCTGTGAAGAGCAGATTCACCATCTCCAAAGAAAATGCCAAGAACTCACTCTGTTTGCAAATGAACAGTCTGAGAGA AGAGGGCACGGCCGTGTATTACTGTATGTGAGT SEQ ID NO: 465 IGHV3-57*01 GAACAGCCTGAGAGCCGAGGGCACAAATTAACAGTCCCAAGCGACACCTTTTCATGTGCAGTCTACCTTACAATGACCAACCTGAA AGCCAAGGAACAAGGCTGTGTATTACTGTGAGGGA SEQ ID NO: 466 IGHV3-57*02 GAGTTACTCTCCATGAGTACAAATAAATTAACAGTCCCAAGCGACACCTTTTTCATGTGCAGTCTACCTTACAATGACCAACCTGAAAG CCAAGGACAAGGCTGTGTATTACTGTGAGGGA SEQ ID NO: 467 IGHV3-6*01 CTACGCAGACTCTGTGAAGGGCCGATTCACCATTTCCAGAGACAATACCAAAAACTCACTGTATCTGAAATGAACAGACTGAGGG CAGAGGATGCAGCTGCATATGACTCTGTGAGAGA SEQ ID NO: 468 IGHV3-60*01 CTACACAGACTCTGTGAAGGGCTGATTCACCATCTCTAGAGACAATGCCCAGAATTCACTGTATCTGCAAATGAACAGCCTGAGAGC CGACGACATGGCTGTGTATTACTGTGTGAAAGA SEQ ID NO: 469 IGHV3-62*01 CTACACAGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAATGCCCAGAATTCACTGTCTCTGCAAATGAACAGCCTGAGAGC CGAGGGCACAGTTGTGTACTACTGTGTGAAAGA SEQ ID NO: 470 IGHV3-63*01 ATGCAGACTCTGTGAAGGGCAGATTCACCATCTCCAAAGACAATGCTAAGAACTCACCGTATCTCCAAACGAACAGTCTGAGAGCT GAGGACATGACCATGCATGGCTGTACATAAGGTT SEQ ID NO: 471 IGHV3-64*01 ATTTCATGCAAACTCTGTGAAGGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACACTGTATCTTCAAATGGGCAGCCTGAG AGCTGAGGACATGGCTGTGTATTACTGTGCGAG SEQ ID NO: 472 IGHV3-64*02 TTATGCAGACTCTGTGAAGGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGGGCAGCCTGAGAG CTGAGGACATGGCTGTGTATTACTGTGCGAGAGA SEQ ID NO: 473 IGHV3-64*03 CTACGCAGACTCAGTGAAGGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATGTCCAAATGAGCAGTCTGAGAG CTGAGGACACGGCTGTGTATTACTGTGTGAAAGA SEQ ID NO: 474 IGHV3-64*04 CATTCTACGCAGACTCCGCGAAGGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACTCTGCATCTTCAAATGAACAGTCTGA GACCTGAGGACTCGGCTGTCTATTACTGTGTGA SEQ ID NO: 475 IGHV3-64*05 ACTACGCAGACTCCGTGAAGGGCAGATTCACCGTCTCCAGAGACGATGCCACGAAGACCCTCTTTCTTCAAGTGAGCGGTCTGCGA GCTGAGGACACGGCTGTCTATTACTGCGTGAAAG SEQ ID NO: 476 IGHV3- AAGTACGCGGACTCCGTGAAGGGCAGATTCATTACCTCCAGAGACAATTCCAAGAACACGTTGTATCTTCAAATGAGCAGTCTGAG 64D*06 ACCTGAGGACACGGCTATTTATTATTGTGTGAAA SEQ ID NO: 477 IGHV3-65*01 CTTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCATCTCTGGGCTCCAGGCTGAGGACGGGGCTGATTATT TCTGCAGCTCATATACAACCAACAACAAGGGG SEQ ID NO: 478 IGHV3-65*01 ATACGCCGCGTCTGTGAAAGGCAGATTCACCATCTCAAGCGATGATTCCAAAAGCATCGCCTATCTGCAAATGAACAGCCTGAAAAC CGAGGACACGGCCGTGTATTACTATACCAGAGA SEQ ID NO: 479 IGHV3-66*01 CTACGCAGACTCCGTGAAGGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAG CCGAGGACACGGCTGTGTATTACTGTGCGAGAGA SEQ ID NO: 480 IGHV3-66*02 TATTACACAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGA GCTGAGGACACGGCTGTGTATTACTGTGCGAGA SEQ ID NO: 481 IGHV3-66*03 CTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAG CTGAGGACACGGCTGTGTATTACTGTGCGAGAGA SEQ ID NO: 482 IGHV3-66*04 CTACGCAGACTCCGTGAAGGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAG CCGAGGACACGGCTGTGTATTACTGTGCGAGACA SEQ ID NO: 483 IGHV3-69 GGGGTTTCTAATCGCTTCTCTGGCTCCAAGTCTGCCAACACGGCCTCCCTGACAATCTCTGGACTCCAGGCTGAGGACGAGGCTGAT 1*01 TATTACTGCTGCTCATATGCAGGAAGTAAGACT SEQ ID NO: 484 IGHV3-69 CATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCAGCATCAGCAGGCTGGAGCCTGAAGACTTTGCAGTGT 1*02 ATTACTGTCAGCAGTATGGTAGCTCACCTCCGGA SEQ ID NO: 485 IGHV3-7*01 CTATGTGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGAGAG CCGAGGACACGGCTGTGTATTACTGTGCGAGAGA SEQ ID NO: 486 IGHV3-7*02 ATACTATATGGACTCTCTGAAGGGCCGATTCACCATCTCCAGAGACAACGCAAGAACTCAGTGAATCTCCAAATCAACAGCCTGAG AGGCGAGGACACGGCTGTCTATTACTGTGCGAG SEQ ID NO: 487 IGHV3-7*03 CTATGTGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGAGGG CCGAGGACACGGCCGTGTATCACTGTGCGAGAGA SEQ ID NO: 488 IGHV3-71*01 GAATAGACCACGTCTGTGAAAGGCAGATTCACAATCTCAAGAGATGATTCCAAAAGCATCACCTATCTGCAAATGAACAGCCTGAG AGCCGAGGACACGGCCGTGTATTACTGTGCGAGA SEQ ID NO: 489 IGHV3-71*02 ATAGACCACGTCTGTGAAAGGCAGATTCACAATCTCAAGAGATGATTCCAAAAGCATCACCTATCTGCAAATGAACAGCCTGAGAG CCGAGGACATGGCTGTGTATTACTGTGCGAGAGA SEQ ID NO: 490 IGHV3-71803 ATAGACCACGTCTGTGAAAGGCAGATTCACAATCTCAAGAGATGATTCCAAAAGCATCACCTATCTGCAAATGAACAGCCTGAGAG CCGAGGACACGGCTGTGTATTACTGTGCGAGAGA SEQ ID NO: 491 IGHV3-72*01 AATACGCCGCGTCTGTGAAAGGCAGATTCATCATCTCAAGAGATGATTCAAAGAACTCACTATATCTGGAAATGAACAGCCTGAAA ACGAGGACACGGCCGAGTATTACTGTGCTAGAG SEQ ID NO: 492 IGHV3-73*01 ACATCTTACGCTCCGTCGATAAAAGGCAAGTTCATCATTTCCAGAGATGATTCCAGCAATATGTTGTATCTTCAAATGAACAACCTGA AAACCGAGGACACGGCCGTCTATTTTTGTACT SEQ ID NO: 493 IGHV3-73*02 GCATATACTGCGTCGGTGAGAGGCAGGTTCACCATCTCCAGAGATGATTCAAAGAACACGGCGTGGCTGCAAATGAGCAGCCTGG AAACCGAGGACACGGCCGTATATTACTGTATTAGA SEQ ID NO: 494 IGHV3-74*01 CTACGCGGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACACGCTGTATCTGCAAATGAACAGTCTGAGAG CCGAGGACACGGCTTTGTATTACTGTGTAAGAGA SEQ ID NO: 495 IGHV3-74*02 AACTACGCGGACTCCGTGAAGGGCCGATTCACCATCTACAGAGACGACGCCAAGAACACACTGAATCTGCAAATGAACAGTCTGAG AGTCGAGGACACGGCAGTGTATTATTGTGTAAGA SEQ ID NO: 496 IGHV3-74*03 AACTTACGCGGACTCCATGAAGGGCCGATTCACCATCTCCAGAGACAATGCCAAAAACACGCTGGATCTGCAAATGAACAGCCTGA GAGTCGAGGACACGGCTGTGTATTACTGTGTAAG SEQ ID NO: 497 IGHV3-75*01 TCCTACTAGCCTGTGGCAAATGGAAGCATCTCTTTTTTATCAGACTGAATAATATTGTAGTGTTTTCTTATACCACATTTACTTCATCCC TTTGTGCATTAACACTTAGGTTGTTTTTAT SEQ ID NO: 498 IGHV3-76*01 TACTACTCAGACTCTGTGAAGGGCCGGTTGACCATCTCCAGAGAAAACACCAAGAACTCACTGTATCTGCAAATAAACAGTTTCATT GCTGACACCATGGCCGTCTATTACTGTAAGAGA SEQ ID NO: 499 IGHV3-79*01 TACCACCCACTCCTCAAGTGTCCAGTCACCATCCCCAGATCCGTGTCCAAAAAAGCAGTTCTTCCTACAGCTGAGCTACATGAGCAAC AAGCACATAGCCATGTATTTTTAAGCCAAAGA SEQ ID NO: 500 IGHV3-9*01 TAGGCTATGTGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACTCCCTGTATCTGCAAATGAATAGTCTGA GAGCTGAGGACACGGCCTTATATTACTGTGCAA SEQ ID NO: 501 IGHV3-9*02 ATGCGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACTCCCTGTATCTGCAAATGAACAGTCTGAGAGCT GAGGACACGGCCTTGTATTACTGTGCAAAAGATA SEQ ID NO: 502 IGHV3-9*03 ATGCGGACTCTGTGAAGGGCCGATTCACCATCGCCAGAGACAACGCCAAGAACTCCCTGTATCTGCAAATGAACAGTCTGAGAGCT GAGGACATGGCCTTGTATTACTGTGCAAAAGATA SEQ ID NO: 503 IGHV4/OR15- CTACAACCCGTCCCTCAAGAGTCGAGTCACCATATCAGTAGACAAGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGC 8*01 CGCGGACACGGCCGTGTATTACTGTGCGAGAGA SEQ ID NO: 504 IGHV4/OR15- TACTACGCAGACTCTGTGAAGGGCCGATTCACCATCTCCAGGGACAACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGAG 8*02 AGCCGAGGACACGGCCGTGTATTACTGTGCGAGA SEQ ID NO: 505 IGHV4/OR15- CTACAACCCATCCCTCAAGAGTCGAGTCACCATATCAGTAGACAAGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGC 8*03 CGCGGACACGGCCGTGTATTACTGTGCGAGAGA SEQ ID NO: 506 IGHV4-28*01 TACTACAACCCGTCCCTCAAGAGTCGAGTCACCATGTCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACC GCGTGGACACGGCCGTGTATTACTGTGCGAGA SEQ ID NO: 507 IGHV4- CTACAACCCGTCCCTCAAGAGTCGAGTCACCATGTCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGC 28*02_IGHV4- CGTGGACACGGCCGTGTATTACTGTGCGAGAAA 28*05_IGHV4- 28*07 SEQ ID NO: 508 IGHV4-28*03 CTACAACCCGTCCCTCAAGAGTCGAGTCACCATGTCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGC CGTGGACACGGCCGTGTATTACTGTGCGAGAGA SEQ ID NO: 509 IGHV4-28*04 TACTACAACCCGTCCCTCAAGAGTCGAGTCACCATGTCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACC GCCGTGGACACCGGCGTGTATTACTGTGCGAGA SEQ ID NO: 510 IGHV4-28*06 CTACAACCCGTCCCTCAAGAGTCGAGTCACCATGTCAGTAGACACGTCCAAGAACCAGTTCTCCCFTGAAGCTGAGCTCTGTGACCGC CTTGGACACGGCCGTGTATTACTGTGCGAGAAA SEQ ID NO: 511 IGHV4-30- ACTTCAACCCGTCCCTCAAGAGTCGAGTCACCCTATCAGTTGACAGGTCCGAGAACCAGTTCTCCCTGAAGCTCAGCTCTGTGACCG 2*01 CCGCGGACACGGCCGTGTATTACTGTGCCAGAG SEQ ID NO: 512 IGHV4-30- CTACAACCCGTCCCTCAAGAGTCGAGTCACCATATCCGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGC 2*03 TGCAGACACGGCTGTGTATTACTGTGCGAGACA SEQ ID NO: 513 IGHV4-30- CTACAACCCGTCCCTCAAGAGTCGAGTTACCATATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACTGC 2*05 CGCAGACACGGCCGTGTATTACTGTGCCAGAG SEQ ID NO: 514 IGHV4-30- CTACAACCCGTCCCTCAAGAGTCGAGTCACCATATCAGTAGACAGGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGC 2*06 CGCGGACACGGCCGTGTATTACTGTGCCAGAGA SEQ ID NO: 515 IGHV4-30 CTACAACCCGTCCCTCAAGAGTCGAGTTACCATATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACTGC 4*02 AGCAGACACGGCCGTGTATTACTGTGCCAGAGA SEQ ID NO: 516 IGHV4-30 ATTATAACCCGCCCCTCAGGAGTCGAGTAACCATATCAGCAGACACGTCCAAGAATCAGGTCTCCCTGGAGCTGAGTCCTATGACTG 4*03 CCGCGGACACGGCCGTGTATTACTGTGCCAGAG SEQ ID NO: 517 IGHV4-30 CTACAACCCGTCCCTCAAGAGTCGAGTTACCATATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGC 4*07 CGCGGACACGGCCGTGTATTACTGTGCCAGAGA SEQ ID NO: 518 IGHV4-31*01 CCTACTACAACCCGTCCCTCAAGAGTCTAGTTACCATATCAGTAGACACGTCTAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGAC TGCTGCGGACACGGCCGTGTATTACTGTGCGA SEQ ID NO: 519 IGHV4-31*02 CTACAACCCGTCCCTCAAGAGTCGAGTTAACCATATCAGTAGACACGTCTAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACTGC CGCGGACACGGCCGTGTATTACTGTGCGAGAGA SEQ ID NO: 520 IGHV4-31*03 TTACTACAACCCCTCCCTCAAGGGGCGAGTTACCATATCAGTAGACACGTCTGAGAACCAGTTCTCCCTGAGGCTGAGCTCTGTGAC TGCCGCGGACACGTCCGTGTATTACTGTGCGAG SEQ ID NO: 521 IGHV4-31*04 ACCGACTACACCCGTCCCTCAGGAGTCGAGTTACCATATCAGTAGACATGTCTAAGAACCAGTTCTCCCTGAAACTGAGGTCTGTG ACTGCCGCGGACGCGGCCGTCTATTATTGTGCG SEQ ID NO: 522 IGHV4-31*06 ACTACAACCCGTCCCTCAAGAGTCGAGTTACCATATCAGTAGACACGCCTAAGAACCAGTTCTCTCTGGAGTTGAGCTCTGTGACTG CCGCGGACACGGCCATATATTACTGTGCAAGAG SEQ ID NO: 523 IGHV4-31*07 ACTATAACCCGGCTCTCAAGAGTCGAGCCTCCATCTCACAAGACACGTCTGAGAACCGGTTTTCCCTGAGGCTGACCTCTGTGACTG CCGCGGACACGGCCGTGTATTTCTGTGCGAGAG SEQ ID NO: 524 IGHV4-31*08 ACTACAACTCGTCCCTCAAGAGTCGACTTACCATATCCGTAGACACGTCCGAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCG CTGCGGACACGGCCGTGTATTACTGTGCGAGA SEQ ID NO: 525 IGHV4-31*10 CTACAACCCGTCCCTCAAGAGTCGAGTTACCATATCAGTAGACCCGTCCAAGAACCAGTTCTCCCTGAAGCCGAGCTCTGTGACTGC CGCGGACACGGCCGTGGATTACTGTGCGAGAGA SEQ ID NO: 526 IGHV4-34*01 ACTACAACCCGTCCCTCAAGAGTCGAGTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCG CCGCGGACACGGCTGTGTATTACTGTGCGAGAG SEQ ID NO: 527 IGHV4-34*02 GACTACAACCCGTCCCTCAAGAGTCGAGTCACCATATCAGTGGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACC GCCGCGGACACGGCTGTGTATTACTGTGCGAGA SEQ ID NO: 528 IGHV4-34*03 ACTACACCCGTCCCTCAAGAGTCGAGTTACCATATCAGTAGACACGTCTAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACTG CCGCGGACACGGCCGTGTATTACTGTGCGAGAG SEQ ID NO: 529 IGHV4-34*04 GAGTTCCTGATCGCTTCTCAGGCTCCAGCTCTGGGGCTGACCGCTACCTCACCATCTCCAACCTCCAGTCTGAGGATGAGGCTGATT ATTACTGTGAGACCTGCGACAGTAACACTCATG SEQ ID NO: 530 IGHV4-34*05 CAACACCCGTCCCTCAAGAGTCGAGCCACCATATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGC CGCGGACACGGCTGTGTATTACTGTGCGAGAGG SEQ ID NO: 531 IGHV4-34*08 ACCAACTACAAAGTTTCCCTCGAGAGTCGAGTCACCATATACATTGACACGTCTAAGAACCGATTCTCCCTGAGGGTGAGGGCCGTG ACCGCCGCGGACACGGCTAAATACTTCTGTGCG SEQ ID NO: 532 IGHV4-34*09 AAGTACAACCCGTCGCTCGAGAGTCGGGTCACCATATCAATAGACACGTCCAGGAACCACTTCTCCCTGAACCTGAGCTCAGTGACC GCCGCGGACACAGCTGTCTATTACTGTGCGAGA SEQ ID NO: 533 IGHV4-34*10 AACTACAACCCGTCCCTCAAGAGTCGAGTCACCATATCAATAGACACGTCCAAGAGGCAATTCTCCCTGAGGCTGACTTCTATGACC GCCGCGGACACGGCTGCATATTTCTGTGCGAGA SEQ ID NO: 534 IGHV4-34*11 ATCCCAGCCAGGCTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGCCTGGAGCCTGAAGATTTTTGCAGTTTAT TACTGTCAGCAGCGTAGCAACTGGCTAATCGCC SEQ ID NO: 535 IGHV4-34*12 TTACAACCCGTCCCTCGAGAGTCGAGTCACCATATCAATAGACACGTCCAAGCACCAATTCTCCCTGAGGGTGATTTCTTTGACCGCC GCGGACACGGCTAGATATTTCTGTGCGAGAGG SEQ ID NO: 536 IGHV4-34*13 ACTACAACCCGTCCCTCAAGAGTCGAGTCACCATATCAGTAGACACGTCCAAGAAACAGCTCTCCCTGAAGTTGAGCTCTGTGAACG CCGCGGACACGGCTGTGTATTACTGTGCGAGAG SEQ ID NO: 537 IGHV4-38 CACTACAACCCGTCCCTCAAGAGTCGAGTCTCCATATCAGTTGTCACGTCCAAGAACCAGCTCTCCCTGAGGCTGAGGTTTGTGACT 2*01 GCCGCAGACACGGCCGTCTATTACTGTGCGAGA SEQ ID NO: 538 IGHV4-38- TACTACAACCCGTCCCTCAAGAGTCGAGTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACC 2*02 GCCGCAGACACGGCCGTGTATTACTGTGCGAGA SEQ ID NO: 539 IGHV4-39*01 AGTGGGGTCCCATCAAGGTTCAGTGCCGGTGTGTCTGGGACAGATTTCACCCTCACCATCAGCAGTCTGCAATCTGAAGATTTTGCA ACTTACTATCTGTCAACAGAGTTATAGTCCCCCG SEQ ID NO: 540 IGHV4-39*02 TACTACAATCCCTCCCTCAAGAGCCGAGTCACCATATCCGTAGACACGTTGAAGAATAACTTCTCCCTGAAGCTGAGTTCTGTGACCG CCGCAGACACGGCTGTTTATTACTGTACGAGA SEQ ID NO: 541 IGHV4-39*03 GTCTACAATCCGTCCCTCAAGAGTCGAGTCACCATATCCGTAGACACGTCCAAGAACCTGTTCTCCCTGAAACTGACCTCTGTGACCG CCGCAGACAGGCTGGTATATTTCTGTGCGAGA SEQ ID NO: 542 IGHV4-39*05 CACCTTCTACAACCCGTCCCTCAAGAGTCGAGTCACCATATCCGTGGACACGTCCAAAAACCAGATCTCCCTGAGGCTGAACTCTGT GACCGCCGCAGACGGCTGTGTATTATTGTGC SEQ ID NO: 543 IGHV4-39*06 CTACAACCCGTCCCTCAAGAGTCGAGTCACCATATCAGTAGACACGTCCAAGAACCAGTTCCCCCTGAAGCTGAGCTCTGTGACCGC CGCGGACACGGCCGTGTATTACTGTGCGAGAGA SEQ ID NO: 544 IGHV4-39*07 ACTATAACCCGTCTCTCATGAGTCGAGTCGCCATATCAGTAGACACGTCCAGGAACCAGTTCTTCCTGAAGCTGAACTCTGTGACCG CCGCGGACACGGCCGTTTATTACTGTGCGAGAG SEQ ID NO: 545 IGHV4-4*01 GGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAACT TACTACTGTCCAACAGAGTTACAGTACCCCCCCG SEQ ID NO: 546 IGHV4-4*02 ACTACAACCCGTCCCTCAAGAGTCGAGTCACCATATCAGTAGACAAGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCG CCGCGGACACGGCCGTGTATTACTGTGCGAGAG SEQ ID NO: 547 IGHV4-4*03 CTACAACCCCTCCCTCAAGAGTCGAGTCACCATGTCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGC CGCGGACACGGCCGTGTATTACTGTGCGAGAGA SEQ ID NO: 548 IGHV4-4*07 ACTACAACCCCTCCCTCAAGAGTCGAGTCACCATGTCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCG CCGCGGACACGGCCGTGTATTACTGTGCGAGAG SEQ ID NO: 549 IGHV4-4*08 CTACACCCCTCCCTCAAGAGTCGAGTCACCATATCCGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGC CGCAGACACGGCCGTGTATTACTGTGCGAGAGA SEQ ID NO: 550 IGHV4-55*01 CTACAACCCGTCCCTCAAGAGTCGAATCACCATGTCCGTAGACACGTCCAAGAACCAGTTCTACCTGAAGCTGAGCTCTGTGACCGC CGCGGACACGGCCGTGTATTACTGTGCGAGATA SEQ ID NO: 551 IGHV4-55*02 CTACAACCCGTCCCTCAAGAGTCGAATCACCATGTCAGTAGACACGTCCAAGAACCAGTTCTACCTGAAGCTGAGCTCTGTGACCGC CGCGGACACGGCCGTGTATTACTGTGCGAGATA SEQ ID NO: 552 IGHV4-55*08 CTACAACCCGTCCCTCAAGAGTCGAAT6CACCATGTCAGTAGACACGTCCAAGAACCAGTTCTACCTGAAGCTGAGCTCTGTGAACCGC CGCGGACACGGCCGTGTATTACTGTGCGAGAGA SEQ ID NO: 553 IGHV4-55*09 CTACAACCCGTCCCTCAAGAGTCGAATCACCATGTCCGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGC CGTGGACACGGCCGTGTATTACTGTGCGAGAAA SEQ ID NO: 554 IGHV4- AACTACAACCCCTCCCTCAAGAGTCGAGTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACC 59*01_IGHV4- GCTGCGGACACGGCCGTGTATTACTGTGCGAGA 59*07 SEQ ID NO: 555 IGHV4-59*02 AGTATAACCCCTCCCTCAAGAATCGAGTCACCATATCATTAGACACGTCCGAGAACCAGTTCTCCCTGAAACTCAGCTCTGTGACCGC CGCGGACACGGCCGTATTACTGTGCCAGAG SEQ ID NO: 556 IGHV4-59*03 ACTACAACCCCTCCGTCAAGAGTCGGGTCACCATATCAGCGCACACGTCCACGAATCAATTCTCCCTGAACCTGTTCTCTGTGACCGC TGCGGACACGGCCGTGTATTACTGTCGAGAG SEQ ID NO: 557 IGHV4-59*04 AAGTATAACCCGTCCCTCAAGAGTCGACTCACCCTGTCCATTGACACGTCCAAGAGCCAGTTCTCCCTGAAGTTGAGGTCTGTGACC GCCGCCGACACGGCCGTCTATTACTGTGCGCGA SEQ ID NO: 558 IGHV4-59*08 CTTTATAATCCCTCCCTCGAGAGTCGAGTCACCATGTCAGTAGACACATCCAAGGACCAGTTCTCCATGAAGCTGACCTCTGTGACCG CCGCAGACACGGCCATATATTACTGTGCGAGA SEQ ID NO: 559 IGHV4-59*10 CAGTTCTCCCTCCCTCAGGAGGCGAGTCACCATGTCAACAGACACGTCCAGAAATCAGTTCTCCCTCAATTTGACTTCTGTGACCGCT GCGGACACGGCCGTCTATTACTGTGCGAGAGA SEQ ID NO: 560 IGHV4-61*01 CTACAACCCCTCCCTCAAGAGTCGAGTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGC TGCGGACACGGCCGTGTATTACTGTGCGAGAGA SEQ ID NO: 561 IGHV4-61*02 CAACTACAACCCCTCCCTCAAGAGTCGAGTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGAC CGCCGCAGACACGGCCGTGTATTACTGTGCGAG SEQ ID NO: 562 IGHV4-61*03 AACTACAACCCCTCCCTCAAGAGTCGAGTCACCATGTCAGTAGACACGTCCAGGAACCACTTCTCCCTGAACCTGAACTCTGTGACC GCCGCAGACACGGCCGTCTATTACTGTGCGAGA SEQ ID NO: 563 IGHV4-61*04 GGGTACACCAGGTACACCCCTCCCTCAAGAGTCGAGTCACCATATCAATAGACTCGTCCAAGAACCAGTTGTCCCTGAATCTGAAC TCTGTGACCGCCGCCGACACGGCCGTCTACTAC SEQ ID NO: 564 IGHV4-61*05 AACTACAACCCCTCCCTCAAGAGTCGAGTCACCATATCAGTAGACAAGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACC GCCGCGGACACGGCCGTGTATTACTGTGCGAGA SEQ ID NO: 565 IGHV4-61*08 AACTACAACCCCTCCCTCAAGAGTCGAGTCAGCATATCAGTAGACGCGTCTAAGAACCAATTCTCCCTGAAGCTGACCTCTGTGACC GCTGCGGACACGGCCGTCTATTACTGTGCGAGA SEQ ID NO: 566 IGHV4-80*01 ATTGGATACATCTATTATAGTGGGAGGAGCTACTACACCCCGTCCCTCAGGAGTTGAGTCACCATGTCAATGAAACGTCCAAGAAC CAGTTTTCCCTGAAGCTGAGCTCTGTGACCGCA SEQ ID NO: 567 IGHV4-10 AACTACAGCCCGTCCTTCCAAGGCCACGTCACCATCTCAACTGACAAGTCCATCAACACTGCCTACCTGCAGTGGAACAGCCTGAAG 1*01 GCCTCGGACACCGCCATCTATTATTGTGCGAGA SEQ ID NO: 568 IGHV5-10 CAATACAGCCCGTCCTTTCAAGGCCACGTCACCATCTCAGCTGACAAGTCCATCACAACTGCCTACTTGCAGTGGAGCAGCCTGAAG 1*02 GCCTCGGACACCGCCATATATTATTGTGCGAGA SEQ ID NO: 569 IGHV4-10 AACTACAGCCCGTCCTTCCAAGGCCACGTCAGCATCTCAGCTGACAAGTCCATCAGCACTGCCTACCTGCAGTGGAGCAGCCTGAAG 1*03 GCCTCGGACACCGCCATGTATTACTGTGCGAGA SEQ ID NO: 570 IGHV5-10 TACAGCCCATCTCTGGAGGGTAGACTCACCATCACTAAGGACACCTCCAAAAACCAGGTGGTCCTTACAATGACCGACATGGACCCT 1*04 GTGGACACAGGCACATATTACTGTGCACACAGA SEQ ID NO: 571 IGHV5-51*01 ATATAGCCCGTCCTTCCAAGGCCAGGTCACCATGTCAGCCGACAAGTCCATCAGCACCGCCTACCTACAGTGGAGCAGCCTGCGGG CCTCGGACACCGCCATGTATTACTGTGCGAGACA SEQ ID NO: 572 IGHV5-51*02 GATACAGCCCGTCCTTCGAAGGCCAGGTCACCATGTCAGCCGACGAGTCCCTTCAGCACCGTCTACCTCCAATGGAGCAGCCTGAAG CCCTCGGACAGCGCCATGTATTTCTGTGCGCGGC SEQ ID NO: 573 IGHV5-51*03 AGATACAGCCCGTCCTTCCAAGGCCAGGTCACCATCTCAGCCGACAAGTCCATCAGCACCGCCTACCTGCAGTGGAGCAGCCTGAA GGCCTCGGACACCGCCATGTATTTCTGTGCGAGA SEQ ID NO: 574 IGHV5-51*04 AGATATAGCCCGTCCTTCCAAGGCCAGGTCACCATCTCAGCCGACAAGCCCATCAGTACCGCCTACCTGCAGTGGAACAGCCTGAG GGCCTCGGACACCGCATTTATTACTGTGCGAGA SEQ ID NO: 575 IGHV5-78*01 ATACAGCCCATCCTTCCAAGGCCACGTCACCATCTCAGCCGACAGCTCCAGCAGCACCGCCTACCTGCAGTGGAGCAGCCTGAAGG CCTCGGACGCCGCCATGTATTATTGTGTGAGAGG SEQ ID NO: 576 IGHV5-78*02 CAGATACAGCCCACCTTCCAAGGCCACGTCACCATCTCAGCCGACAGCTCCAGCAGCACCGCCTACCTGCAGTGGAGCAGCCTGAA GGCCTCGGACGCCGCCATGTATTATTGTGTGAGA SEQ ID NO: 577 IGHV6-1*01 ATTATGCAATATCTGTGAAAAGTCGAATAGCCATCAACCCAGACACATCCAAGAACCAGTTCTCCCTGCAGCTGAACTCTGTGACTC CCGAGGACACGGCTGTGTATTACTGTGCAAGAG SEQ ID NO: 578 IGHV6-1*02 ATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTA TTACTGTCAGCAGTGTAGTAGCTCACCCTGGATG SEQ ID NO: 579 IGHV7-27*01 ACTGGGAACCTAACGTATGCCCAGGGCTTCACAGGACGGTTTGTCTTCTCCATGGACACCTCCGTCAGCATGGCATATCTTCATATC AGCAGCCTAAAGGCTGAGGACACGTGCAAGAGG SEQ ID NO: 580 IGHV7-34- GTATACCCACGGCTTCACAGGATGGTTTGTCTTCTCCATGGACACGTCTGTCAGCACGGCGTGTCTTCAGATCAGCAGCCTAAAGGC 1*01_IGHV70 TGAGGACACGGCCGAGTATTACTGTGCGAAGTA 34-1*02 SEQ ID NO: 581 IGHV7-40*01 CCTGACCGCTTCTCTGGCTCCAAGTCTGGCACGTCTGCCACCCTGGGCATCACTGGACTCCAGACTGGAGACGAGGCCCATTATTAC TGCGCCACATGGGATAGTGGCCTGAGTGCCGGA SEQ ID NO: 582 IGHV47-40*03 ATATACCACGGCTTCACAGGACGGTTTCTATTCTCCATGGACACCTCTGTCAGCATGGCGTATCTGCAGATCAGCAGCCTAAAGGC TGAGGACACGGCCGTGTATGACTGTATGAGAGA SEQ ID NO: 583 IGHV47-40*04 ATATACCACGGCTTCACAGGACGGTTTCTATTCTCCATGGACACCTCTGTCAGCATGGCGTATCTGAAGATCAGCAGCCTAAAGGC TGAGGACACGGCCGTGTATGACTGTATGAGAGA SEQ ID NO: 584 IGHV7- GTATACCCACGGCTTCACAGGACGGTTTGTCTTCTCCATGGACACCTCTGTCAGCATGGCGTATCTGCAGATCAGCAGCCTAAAGGC 40D*01 TGAGGACACGGCCGTGTATGACTCTATGAGAGA SEQ ID NO: 585 IGHV7-4- ACGTATGCCCAGGGCTTCACAGGACGGTTTGTCTTCTCCTTGGACACCTCTGTCAGCACGGCATATCTGCAGATCTGCAGCCTAAAG 1*01 GCTGAGGACACTGCCGTGTATTACTGTCGAGA SEQ ID NO: 586 IGHV7-4- CAACATATGCCCAAGACTTCACAGGGCGATTTGTCTTCTCCCTGGACACCTCTGTCAACACGGCATTTCTGCAGATCAGCAGCCTACA 1*02 GGCTGAAGACACTGCCGTCTATTACTGTGCA SEQ ID NO: 587 IGHV7-4- GTATGCCCAGGGCTTCACAGGACCGGTTTGTCTTCTCCTTGGACACCTCTGTCAGCATGGCATATCTGCAGATCAGCAGCCTAAAGGC 1*04 TGAGGACACTGCCGTGTATTACTGTGCGAGAGA SEQ ID NO: 588 IGHV7-4- GTATGCCCAGGGCTTCACAGGACGGTTTGTCTTCTCCTTGGACACCTCTGTCAGCATGGCATATCTGCAGATCAGCAGCCTAAAGGC 1*05 TGAGGACACTGCCGTGTGTTACTGTGCGAGAGA SEQ ID NO: 589 IGHV7-56*02 TGTATGCCCACAGATTCACACACGGTTTGTCTTCTCCATGGACACCTCTGTCAGCACGGCGGATCTGCAGACTAGCTGCCTAAAGAC TGAGGATGCAGCCATTTATTACTGTGTGAGGTA SEQ ID NO: 590 IGHV7-81*-01 ATATGCCCAGGGCTTCACAGGACGGTTTGTCTTCTCCATGGACACCTCTGCCAGCACAGCATACCTGCAGATCAGCAGCCTAAAGGC TGAGGACATGGCCATGTATTACTGTGCGAGATA SEQ ID NO: 591 IGK1/OR10- TGGGATTCCCTCTCGGTTCAGTGACAGTGGATCTGGGACAGATTACACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAAC 1*01_IGKV1/ TTATTACTGTCAACAGAGTGACAGTACCTCTCC OR10-1*01 SEQ ID NO: 592 IGKV1/OR1- TGGGATTCCCTCTCGGTTCAGTGACAGTGGATCTGGGGCAGACTACACTCTCACCATCCGCAGCCTGCAGCCTGAAGATTTTGCAAG 1*01 TTATTACTGTCAACAGAGTGACAGTACCCCTCC SEQ ID NO: 593 IGKV1/OR15- TGGGATTCCCTCTCGGTTCAGTGACAGTGGATCTGGGGCAGATTACACTCTCACCATCCGCAGCCTGCAGCCTGAAGATTTTGCAAC 118*01 TTATTAGTGTCAACAGAGTGACAGTACCCCTCC SEQ ID NO: 594 IGKV1/OR- TGGGATTCCCTCTCGGTTCAGTGACAGTGGATCTGGGACAGATTACACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAAC 2*01 TTATTACTGTCAACAGAGTGACAGTAACCCTCC SEQ ID NO: 595 IGKV1/O42- TGGGATTCCCTCTCGGTTCAGTGACAGTGGATCTGGGGCAGATTAACTCTCACCATCCGCAGCCTGCAGCCTGAAGATTTTGCAAC 0*01 TTATTACTGTCAACAGAGTGACAGTACCCCTCC SEQ ID NO: 596 IGKV1/OR2- TGGGATTCCCTCTCGGTTCAGTGACAGTGGATCTGGGGCAGATTACACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAGC 1*01_IGKV1/ TTATTACTGTCAACAGAGTGACAGTACCCCTCC OR2-2*01 SEQ ID NO: 597 IGKV1/OR2- GGGGGTCCCATCTCGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATGTTGCAA 108*01 CTTATTACTGTCTACAGGATTATACTACCCCATT SEQ ID NO: 598 IGKV1/OR2- GGCGATGCCATCTCAGTTCAGTGGCAGCGGATATGGAAGAGATTTCACTCTCACCGTCAGCAGCCTGCAGCCTGAAGATTTTGCAA 11*01_IGKV1/ CTTATTAATGTCAACAAGAGAGCATTTTCCCTCC OR2-9*01 SEQ ID NO: 599 IGKV1/OR2- TGGGATTCCCTCTCGGTTCAGTGACAGTGGATCTGGGGCAGATTACACTCTCACCATCCGCAGCCTGCAGCCTGAAGATTTTGCAAA 118*01 TTATTACTGTCAACAGAGTGACAGTACCCCTCC SEQ ID NO: 600 IGKV1/OR22- CCATCCTGGTTCAGTAGCAGTCAATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGCAGCGTGATGATTTGGCCAC 1*01 TTATTACTATCAACAGCATTACAGTTACCCTCC SEQ ID NO: 601 IGKV1/OR22- TGGGATTCCCTCTCAGTTCAGTGACAGTGGATCTGGGACAGATTAGACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAAC 5*01 TTATTACTGTCCAACAGAGTTACAGTACCCCTCC SEQ ID NO: 602 IGKV1/OR22- TGGGATTCCCTCTCAGTTCAGTGACAGTGGATCTGGGACAGATTAGACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTACAAC 5*02 TTATTACTGTCAACAGAGTTACAGTACCCCTCC SEQ ID NO: 603 IGKV1/OR2- GGGGATGCCATCTCAGTTCAGTGGCAGCGGATATGGAAGAGATTTCACTCTCACTGTCAGCAGCCTGCAGCCTGAAGATTTTGCAA 3*01 CTTATTAATGTCAACAAGAGAGCATTTTCCCTCT SEQ ID NO: 604 IGKV1/OR2- GTTTGCAAACGGGGGTTCCATCTCTGTTCAGTGGTAGTGAATCTGGGACAGATTTCACTCTAACCATCAGCAGCCTGCAGCCTGATG 6*01 ATGATGCAACTTACTACTGTCAACAGTAACTCC SEQ ID NO: 605 IGKV1/OR- TGGGATTCCCTCTCGGTTCAGTGACAGTGGATCTGGGACAGATTACACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAGC 3*01 TTATTACTGTCAACAGAGTGACAGTACCCCTCC SEQ ID NO: 606 IGKV1/OR9- TGGGATTCCCTCTCGGTTCAGTGACAGTGGATCTGGGACAGATTACACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAAC 1*01_IGKV1/ CTATTACTGTCAACAGAGTGACAGTAACCCTCC OR9-2*01 SEQ ID NO: 607 IGKV1/ORY- TGGGATTCCCACTCGGTTCAGTGACAGTGGATCTGGGACAGATTACACTCCCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAAC 1*01 TTACTACTGTCAACAGAGTGACAGTACCCCTCC SEQ ID NO: 608 IGKV1-12*01 TGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAAC TTACTATTGTCAACAGGCTAACAGTTTCCCTCC SEQ ID NO: 609 IGKV1-12*02 TGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAAC TTACTATTGTCAACAGGCTAACAGTTTCCCTTC SEQ ID NO: 610 IGKV1- TGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAAC 13*01_IGKV1D- TTATTACTGTCAACAGTTTAATAATTACCCTA 13*01 SEQ ID NO: 611 IGKV1- TGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAAC 13*02_IGKV1D- TTATTACTGTCAACAGTTTATAGTTACCCTCA 13*02 SEQ ID NO: 612 IGKV1-16*01 AGTGGGGTCCCATCCAGGTTCAGTGGCAGTGGATCTGGGACGGATTACACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGC AACTTATTACTGTCAACAGTATTATAGTACCTCT SEQ ID NO: 613 IGKV1-16*02 AAGTGGGGTCCCATCAAAGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTG CAACTTATTACTGCCAACAGTATAATAGTTACCC SEQ ID NO: 614 IGKV1-17*01 AGGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACAATCAGCAGCCTGCAGCCTGAAGATTTTG CAACTTATTACTGTCTACAGCATAATAGTTACCC SEQ ID NO: 615 IGKV1-17*02 TGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACAATCAGCAACCTGCAGCCTGAAGATTTTGCAA CTTATTACTGTCTACAGCATAATAGTTACCCTCC SEQ ID NO: 616 IGKV1- TGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACAATCAGCAGCCTGCAGCCTGAAGATTTTGCAA 17*03_IGKV1D- CTTATTACTGTCTACAGCATAATAGTTACCCTCC 17*01 SEQ ID NO: 617 IGKV1-22*01 GGGTCCCGTCACGGTTCAGTGGCAGTAGGTCTGGGACACATTTCACACATTCTCACCATCAGGAGCCTGCAACCTGAAGATGTTATA ACTTATTGCTGTCTATAGACTTACAGCAGCCAT SEQ ID NO: 618 IGKV1-27*01 ATCAGGGGTCCCATCTCGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATGTTGC AACTTATTACTGTCAAAAATATAACAGTGTCCC SEQ ID NO: 619 IGKV1-32*01 GGGGTCCCTGATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCGTCTCTGGGCTCCAGGCTGAGGATGAGGCTGA TTACTACTGCAGTTCATATGCTGGCGACAACATT SEQ ID NO: 620 IGKV1-33*01 TGAAAACAGGGGTCCCATCAAGGTTCAATGGAAGTGGATCTGGGACAGATTTTACTTTCACCATCAGCAGCCTGCAGCCTGAAGAT ATTGCAACATATTACTGTCAACAGTATGATAATC SEQ ID NO: 621 IGKV1- TGGGGCTCCTTCGCGGTTCGGTGGCAGTGGATCTGGGACAGATTTTACTCTCACCATCAGAATCCTGCAGCCTAAAGATGTTGCAAC 35*01_IGKV1D- TTATTACTGTCAACAGTATAAAAATTACCCTAT 35*01 SEQ ID NO: 622 IGKV1- TGGAGTCCCATCTCGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACTATCAGCAGCCTGCAGCCTGAAGATGTTGCAAC 37*01_IGKV1D- TTATTACGGTCAACGGACTTACAATGCCCCTCC 37*01 SEQ ID NO: 623 IGKV1-39*01 TGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAAC TTACTACTGTCAACAGAGTTACAGTACCCCTCC SEQ ID NO: 624 IGKV1-39*02 TGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAAC TTATTACTGTCAGTGTGGTTACAGTACACCTCC SEQ ID NO: 625 IGKV1-5*01 TGGGGTCCCACCAACCTTCAGCGGCAGTGGATCTGGGACAGAATTCGCTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAA CTTATTACTGCCAACAGTATGATAGTTATTCGAC SEQ ID NO: 626 IGKV1-5*02 TGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAAC TTATTACTGCCAACAGTATAATAGTTATTCTCC SEQ ID NO: 627 IGKV1-5*03 GTCCCTGATCGCTTCTCTGGCTCCATCCTTGGGAACAAAGCTGCCCTCACCATCACGGGGGCCCAGGCAGATGATGATTCTGACTAT TACTGTGTACTATATATGGGTGATGCCTGGGCG SEQ ID NO: 628 IGKV1-6*01 GTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATTTGGCACAGATTTCACTCTCACCATCAGCAGCCTACAGCCTGAAGATTTTGCAA CTTATTACTGTCTACAAGATTACAGTTACCCTC SEQ ID NO: 629 IGKV1-6*02 TGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGCACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAAC TTATTACTGTCTACAAGATTACAATTACCCTCC SEQ ID NO: 630 IGKV1-8*01 GTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCGGCCTGCAGTCTGAAGATTTTGCA ACTTATTACTGTCGACAGTATTATAGTTACCCTC SEQ ID NO: 631 IGKV19*01 TTGGGTCCCATCAAGGTTCAGCGGCCGTGGATCTGGGACCGAATTCACCCTCACAATCAGCAGCCTGCAGCCTGAAGATTTTGCAAC TTATTACTGTCAACAGCTTAATCGTTACCCTCC SEQ ID NO: 632 IGKV1D- AAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACTATCAGCAGCCTGCAGCCTGAAGATTTTG 12*01 CAACTTACTATTGTCAACAGGCTAACAGTTTCCC SEQ ID NO: 633 IGKV1D- AAGTGGGGTCCCGTCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAGGATTTTG 16*01 CGACTTATTACTGCCAACAGTATAATAGTTACCC SEQ ID NO: 634 IGKV1D- TGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAAC 16*02 TTATTACTGCCAACAGTATAATAGTTACCCTCC SEQ ID NO: 635 IGKV1D- AAGTGGGGTCCCATCGAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACAATCAGCAGCCTGCAGCCTGAAGATTTTG 17*02 CAACTTATTACTGTCTACATCATAATAATTACCC SEQ ID NO: 636 IGKV1D- GGGTCCCGTCACGGTTCAGTGGCAGTAGGTCTGGGACACATTTCACACATTCTCACCATCAGGAGCCTGCAACCTGAAGATGTTATA 22*01 ACTTATTACTGTCTATAGACTTACAGCAGCCAT SEQ ID NO: 637 IGKV1D- GGGGGTCCCATCTCGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATGTTGCAA 27*01 CTTATTACTGTCAAAAGTATAACAGTGCCCCTCC SEQ ID NO: 638 IGKV1D- GTCCCATTGCAGTTATGTGGCATTGGATCCAGGACAGATTTGATTCTCACCATTAGCATCCTCCAGTCTGAAGTTGCTGCAACTTCTT 32*01 ATTATTGGTCAACAGTATAAAAGTGACCCTCT SEQ ID NO: 639 IGKV1D- AGCAGGGGTCCCATCAAGGTTCAGTGGAAATAGATCTGGGACAGATTTTACTTTCACCATCAACAGCCTGCAGTCTGGAGATATCG 33*01 CAACATATTACTGTCAACAGTATGATGATCTCCC SEQ ID NO: 640 IGKV1D- AGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCCTCACCATCAACAGTCTGCAACCTGAAGATTTTGCA 39*01 ACTTACTACTGTCAACAGAGTTACAGTACCCCC SEQ ID NO: 641 IGKV1D- TGGGGTCTCATCGAGGTTCAGTGGCAGGGGATCTGGGACGGATTTCACTCTCACCATCATCAGCCTGAAGCCTGAAGATTTTGCAG 42*01_IGKV1D- CTTATTACTGTAAACAGGACTTCAGTTACCCTCC 42*02 SEQ ID NO: 642 IGKV1D- TGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACGGATTACACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAA 43*01 CTTATTACTGTCAACAGTATTATAGTACCCCTCC SEQ ID NO: 643 IGKV1D-8*01 AGTGGGGTCCCATCAAGATTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATTAGTTGCCTGCAATCTGAAGATTTTGCA ACTTATTACTGTCAACAATATTATAATTTCCCT SEQ ID NO: 644 IGKV1D- TGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCTGCCTGCAGTCTGAAGATTTTGCAAC 8*02_IGKV1D- TTATTACTGTCAACAGTATTATAGTTTCCCTCC 8*03 SEQ ID NO: 645 IGKV1- TGGGGTCCCATCCAGGTTCAGTGGCAGTGGATCTGGGACGGATTACACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAA NL1*01 CTTATTACTGTCAACAGTATTATAGTACCCCTCC SEQ ID NO: 646 IGKV2/OR2- GGGTCCCAGACAGGTTCAGTGGCAGTGGGTCAGGCATTGATTTCACACTGAAAATCAGCCCGGTGGAGGCTGAGGATGTTGGGGT 1*01 TTATATTACTGCATGCAAGCTACACACTGGCCCCC SEQ ID NO: 647 IGKV2/OR2- CTGGAGTCCCAGACAGGTTCAATGGCAGTGGGTCAGGCACTGATTTCACACTGAAAATCAGCCGGGTGGAGCTGAAGATGTTGGG 10*01_IGKV2/ GTTTATTACTGCATGCAGGCTCTGCAGCTTCCTCC OR2- 2*01_IGKV2/ OR2-8*02 SEQ ID NO: 648 IGKV2/OR22- TGCAGTCCCAGACAGGCTCAGTGGCAGTGGGTCAGGCACTGATTTCACACTGAAAATCAGCCGGGTGGAGGCTGAAGATGTTGGG 3*01 GTTTATCACTGCATGCAAGCTCTACAAACTCCTCC SEQ ID NO: 649 IGKV2/OR22- TGGAGTTCCAGACAGGTTCAGTGGCAGTGGGTCAGGCACTGATTTCACTCTGAAAATCAGTAGGGTGGAGGCTTAGGATGTTGGG 4*01 GTTTATTACTGCATGCAAGCTCTACAAACTCCGCC SEQ ID NO: 650 IGKV2/OR2- GGGTCCCAGACAGGTTCAGTGGCAGTGGGTCGGGCATTGATTTCACACTGAAAATCAGCCCGGTGGAGGCTGCGGATGTTGGGGT 4*01_IGKV2/ TTATATTACTGCATGCAAGCTACACACTGGTCCCC OR2- 7*01_IGKV2/ OR2-7D*01 SEQ ID NO: 651 IGKV2-10*01 CTGGAGTCCCAGACAGGTTCAGTGGCAGTGGGTTGGGGACAGATTTCATGCTGAAATCAGGAGGATGGATGCTGAGGATGTTGGG GTTTATTGCTGCCAGCAAAGTACACATTATCCTCC SEQ ID NO: 652 IGKV2- TGGAGTCCCAGACAGGTTCAGTGGCAGTGGGTCGGGGACAGATTTCATGTTTAAAATAAGGAGGATGGATGCTGAGGATGTTGGG 14*01_IGKV2D- GTTTATTGCTGCCAGCAAAGTACACATTATTCTCC 14*01 SEQ ID NO: 653 IGKV2-18*01 AATCCCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCATCTCTGGGCTCCAGGCTGAGGACGAGGCTGATTATTACTGC GCCTATATACAAGCAGCAGCACTCTTTATATC SEQ ID NO: 654 IGKV2-19*01 TCTGGGGTCTCGGGCAGGTTCAGCAGCAGTGGTTCAGGGACAGATTTCATATTGAAAATCAGCAGGGTAGAGGCTGAGGACGTTG GGGTTTATTACTGCCTGCAAGGTACACAAGTGCCT SEQ ID NO: 655 IGKV2-23*01 TGGTAATGGATACACCTATTTGTATTAGTTCCTGCAGAAGCCAGGCCACTCTCCACAGCTCCTGATCTGTAGGACTTCCATCAGTTT TCTGCCTTCCCACACAGGTTCTCCCCAGTGGG SEQ ID NO: 656 IGKV2-24*01 CTCTGGGGTCCCAGACAGATTCAGTGGCAGTGGGGCAGGGACAGATTTCACACTGAAAATCAGCAGGGTGGAAGCTGAGGATGTC GGGGTTTATTACTGCATGCAAGCTACACAATTCCC SEQ ID NO: 657 IGKV2-26*01 TGGAGTGCCAGATAGGTTCAGTGGCAGCGGGTCAGGGACAGATTTCACACTGAAAATCAGCCGGGTGGAGGCTGAGGATGTTGG AGTTTATTACTGCATGCAAGATGCACAAGATCCTCC SEQ ID NO: 658 IGKV2-28*01 CGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACACTGAAAATCAGCAGAGTGGAGGCTGAGGATGTTGGG GTTTATTACTGCATGCAAGCTCTACAAACTCCTCC SEQ ID NO: 659 IGKV2-29*01 TGGAGTGCCAGATAGGTTCAGTGGCAGCGGGTCAGGGACAGATTTCACACTGAAAATCAGCCGGGTGGAGGCTGAGGATGTTGG GGTTTATTACTGAATGCAAGGTATACACCTTCCTCC SEQ ID NO: 660 IGKV2- TGGAGTGCCAGATAGGTTCAGTGGCAGCGGGTCAGGGACAGATTTCACACTGAAAATCAGCCGGGTGGAGGCTGAGGATGTTGG 29*02_IGKV2- GGTTTATTACTGCATGCAAGGTATACACCTTCCTCC 29*03 SEQ ID NO: 661 IGKV2-30*01 CTCTGGGGTCCCAGACAGATTCACCGGCAGTGGGTCAGGCACTGATTTCACACTGGAAATCAGCAGGGTGGAGGCTGAGGATGTT GGGGTTTATTACTGCATGCAAGGTACACACTGGCC SEQ ID NO: 662 IGKV2- CTCTGGGGTCCCAGACAGATTCAGCGGCAGTGGGTCAGGCACTGATTTCACACTGAAAATCAGCAGGGTGGAGGCTGAGGATGTT 30*02_IGLV7- GGGGTTTATTACTGCATGCAAGGTACACACTGGCC 46*01 SEQ ID NO: 663 IGKV2-36*01 ATTTATGAGGTTTCCAACCAAGCCTCCGAATTCTCAGACAGGTTCAGGGGTAATGGGTCAGGTACTGAGTTTACACTGAAAGTCAGT AGGACGGAGACCAAGGATGTTGGAGTTTATTAG SEQ ID NO: 664 IGKV2-38*01 TCTGGAGTCCCAGACAGGTTCAATAGCAGTGGGTCAGGCACATATTTTAAACTCAAAATTAGCAGGGTGGAGGCTGAGGATATTCG ACTTTATTAATACATGCAAGCTACATAATATCCT SEQ ID NO: 665 IGKV2-4*01 TGGAGTCCCAAACAAGTTCAGTGGCAGCAGGTCAGGGACAGGTTTCACACTTAAATTCAGCAAAGTGGAGGCTGAGGATGTTGGG GTTTATTGCTGTGAACAGGGTCTGCAAGGTCCTCA SEQ ID NO: 666 IGKV2-40*01 CCTGATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCATCTCTGGGCTCCTGGCTGAAGATGAGGCTGATTATCACT GCTGCTCATATGCGGGCAGCTTCACTGTGATC SEQ ID NO: 667 IGKV2D- CTGGAGTCCCAGACAAGTTCAGTGGCAGTGGGTCGGGGACAGATTTCATGCTAAAATCAGGAGGATGGATGCTGAGGATGTTGGG 10*01 GTTTATTGCTGCCAGCAAAGTACACATTATCCTCC SEQ ID NO: 668 IGKV2D- TCTGGGGTCCCAGACAGGTTTAGTGGCAGTGGGTCAGGCAGTGATTTCACACTGAAAATCAGCTGGGTGGAGGCTGAGGATGTTG 18*01 GGGTTTATTACTGCATGCAAGCTACACAGTTTCCT SEQ ID NO: 669 IGKV2D- GGGGTTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCATCTCTGGCTCCAGGCTGAGGACGAGGCTGAT 19*01 TATTACTGCTGCTCATATGCAAACAGCGACTCC SEQ ID NO: 670 IGKV2D- ACCACATAACCGTGAGTTTGCAGTGGTTGCAGGTCAGGGACAGATTTTATGCTTAAGATCAGTAGGGTGGAGGCTGAGGATCTTGG 23*01 CTATTACAACTGCCACCACACTCTACAATATCCT SEQ ID NO: 671 IGKV2D- TGGGGTCCCAGACAGATTCAGTGGCAGTGGGGCAGGGACAGATTTCACACTGAAAATCAGCAGGGTGGAAGCTGAGGATGTCGG 24*01 GGTTTATTACTGCACGCAAGCTACACAATTTCCTCA SEQ ID NO: 672 IGKV2D- TGGAGTGCCAGATAGGTTCAGTGGCAGCGGGTCAGGGACAGATTTCACACTGAAAATCAGCCGGGTGGAGGCTGAGGATTTTGGA 26*01_IGKV2D- GTTTATTACTGCATGCAAGATGCACAAGATCCTCC 26*03 SEQ ID NO: 673 IGKV2D- TCTGGAGTGCCAGATAGGTTCAGTGGCAGCGGGTCAGGGACAGATTTCACACTGAAAATCAGCCGGGTGGAGGCTGAGGATTTTG 26*02 GAGTTTATTACTGCATGCAAGATGCACAAGATCCT SEQ ID NO: 674 IGKV2D- TCCGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACACTGAAAATCAGCAGAGTGGAGGCTGAGGATGTTG 28*01 GGGTTTATTACTGCATGCAAGCTCTACAAACTCCT SEQ ID NO: 675 IGKV2D- CTCTGGAGTGCCAGATAGGTTCAGTGGCGGCGGGTCAGGGACAGATTTCACACTGAAAATCAGCCGGGTGGAGGCTGAGGATGCT 29*01 GGGGTTTATTACTGCATGCAAAGTATACAGCTTCC SEQ ID NO: 676 IGKV2D- ACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAAGAACACTCTGTATCTGCAAATGAACAGCCTGAGA 29*02 GTCGAGGACACGGCCGTATATTACTGTGCGAAAG SEQ ID NO: 677 IGKV2D- CTGGGGTCCCAGACAGATTCAGCGGCAGTGGGTCAGGCACTGATTTCACACTGAAAATCAGCAGGGTGGAGGCTGAGGATGTTGG 30*01 GGTTTATTACTGCATGCCAAGGTACATACTGGCCTC SEQ ID NO: 678 IGKV2D- TCTTACGCTCCGTCGATAAAAGGCAAGTTCATCATTTCCAGAGATGATTCCAGCAATATGTTGTATCTTCAAATGAACAACCTGAAAA 38*01 CCGAGGACACGGCCGTCTATTTTTGTACTCGC SEQ ID NO: 679 IGKV2D- TGGAGTCCCAGACAGGTTCAGTGGCAGTGGGTCAGGCACTGATTTCACACTGAAAATCAGCAGGGTGGAGGCTGAGGATGTTGGA 40*01 GTTTATTACTGCATGCAACGTATAGAGTTTCCTTC SEQ ID NO: 680 IGKV3/OR22- CCTGGAAAAGCTCCCTGGTTCCTCATCTAAGGCACATCCAACAGGGCCACTAGCATCCTGGGGTTTAGTGGTCATGGATTGGAGAC 2*01 AGACTTTACTATCACCATCAGCTGCCTGAAGCCT SEQ ID NO: 681 IGKV3/OR2- TGGCATCCCAGCCAGGTTCAGTGGTAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAGT 268*01 TTATTACTGTCAGCAGGATTATAACTTACCTCC SEQ ID NO: 682 IGKV3/OR2- TGACATCCCAGTGGGGCTCAGTAGCTGTGAATCTGGGATGTACTTTACTCTCACCAACAGTAACCTGGAACCTGAAGATTTTGCACT 5*01 TGATTACTCTTATCTGTATAGTAGTTGGAATTT SEQ ID NO: 683 IGKV3-11*01 CCGCTGGCGTCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCACCCTAGAACCTGAAGATTTTG CAGTTTATTACTGTCAACACTGTAGGAACTGGC SEQ ID NO: 684 IGKV3-11*02 TACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGACACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGA GCTGAGGACACGGCCGTGTATTACTGTGCGAGA SEQ ID NO: 685 IGKV3-15*01 GGTATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGCAGT TTATTACTGTCAGCAGTATAATAACTGGCCTCCG SEQ ID NO: 686 IGKV3-20*01 CACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTCAAGATTTTG CAGTGTATTACTGTCAGCACTATGGTAGGTCACC SEQ ID NO: 687 IGKV3-20*02 GTGCATCCAGCAGGGCCACTGGCATCCCAGCAAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTG GAGCCTGAAGATTTTGCAGTTTATTACTGTCAGC SEQ ID NO: 688 IGKV3-25*01 TACAGCCCTGATTTGTGATAGTGGGTCGGGGACAGGGCTTACTCTCACCATCGGCAGCCTGGAGCCTGGAGCCTGGAGATTTGCAC TTCATCACTGTTATCAGCATAGTAGTTGGTGTCC SEQ ID NO: 689 IGKV3-31*01 ATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGCCTGGAGCCTGAAGATTTTGCAGTTTAT TACTGTCAGCACCGTAGCAACTGGCTAATCGCC SEQ ID NO: 690 IGKV3- AGCATCCCAGCCCGGTTCAGTGGTGGTGGGCCTGAGGCAGACTTTACCCCAACCATCAACAGCCTAGACCCTGAAGATGTCACAAT 34*01_IGKV3D- TTTATTACCCTCATCAGTACAGCAGTGGGTGTCC 34*01 SEQ ID NO: 691 IGKV3-7*01 TAGCATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAGT TTATTACTGTCAGCAGGATCATAACTTACCTCC SEQ ID NO: 692 IGKV3- TGGCATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAG 7*02_IGKV3/ TTTATTACTGTCAGCAGGATTATAACTTACCTCC OR2- 268*02_IGKV3D- 7*01 SEQ ID NO: 693 IGKV3-7*03 TAGCATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGAGAGACTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAG TTTATTACTGTCAGCAGGATCATAACTTACCTCC SEQ ID NO: 694 IGKV3-7*04 TAGCATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAGT TTATTACTGTCAGCAGGATTATAACTTACCTCC SEQ ID NO: 695 IGKV3D- TGGCATCCCAGCCAGGTTCAGTGGCAGTGGGCCTGGGACAGACTTCACTCTCACCATCAGCAGCCTAGAGCCTGAAGATTTTGCAG 11*01_IGKV3D- TTTATTACTGTCAGCAGCGTAGCAACTGGCATCC 11*02 SEQ ID NO: 696 IGKV3D- TGGCATCCCAGCCAGGTTCAGTGGCAGTGGGCCTGGGACAGACTTCACTCTCACCATCAGCAGCCTAGAGCCTGAAGATTTTGCAG 11*03 TGTATTACTGTCAGCAGCGTAGCAACTGGCATCC SEQ ID NO: 697 IGKV3D- TATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGTAGCCTGCAGTCTGAAGATTTTGCAGTTTA 15*01 TTACTGTCAGCAGTATAATAACTGGCCTCAGAG SEQ ID NO: 698 IGKV3D- TGGCATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGCAG 15*02 TTTATTACTGTCAGCAGTATAATAACTGACCTCC SEQ ID NO: 699 IGKV3D- TGGCATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCATCCTGCAGTCTGAAGATTTTGCAGT 15*03 TTATTACTGTCAGCAGTATAATAACTGGCCTCC SEQ ID NO: 700 IGKV3D- ACTGGCATCTCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGAAGCCTGAAGATTCTGC 20*D1 AGTGTATTTCTGTCAGCAATATGGATCATCCCCT SEQ ID NO: 701 IGKV3D- TGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAG 20*02 TCTATTACTGTCAGCAGCGTAGCAACTGGCATCC SEQ ID NO: 702 IGKV3D- ATCTATGGTACAGCCCTGATTTGTGATAGTGGGTCAGGACAGGGCTTACTCTCACCATCGGCAGGCTGGAGCCTGAAGATTTGCAC 25*01 TTCATCACTGTTATCAGCATAGTAGTTGGTGTCC SEQ ID NO: 703 IGKV3D- CAATGTCCCAGCCTGGTGGAGTGGCAGTGGGTTCGGGGAAAGCTTCAGTCTCATTATCAGCAGGCTGGAGCATGAAGATTTTGCAC 31*01 TTTAACACTGTTATCAGCATAGTGGTGGGTATTC SEQ ID NO: 704 IGKV4-1*01 ATCCGGGGTCCCTGACCGATTCAGTGGCAGCGGGTCTGGGACAGATTTCACTCTCACCATTAGTAGCCTGCAGACTGAAGATGTGG CAGTTTATTCTTGTCAGCAATTTCATAGTTTTCC SEQ ID NO: 705 IGKV5-2*01 CCTGGAATCTCACCTCGATTCAGTGGCAGCGGGTATGGAACAGATTTTACCCTCACAATTAATAACATAGAATCTGAGGATGCTGCA TATTACTTCTGTCTACAACATGATAATTTCCCG SEQ ID NO: 706 IGKV6- AGGGGTCCCCTCGAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACCCTCACCATCAATAGCCTGGAAGCTGAAGATGCTGCAA 21*01_IGKV6- CGTATTACTGTCATCAGAGTAGTAGTTTACCTCA 6- 21*02-IGKV6D- 21*01 SEQ ID NO: 707 IGKV6D- AGGGGTCCCCTCGAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACCCTCACCATCAATAGCCTGGAAGCTGAAGATGCTGCAG 21*02 CGTATTACTGTCATCAGAGTAGTAGTTTACCTCA SEQ ID NO: 708 IGKV6D- TCAGGGGTCCCCTCGAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACCTTTACCATCAGTAGCCTGGAAGCTGAAGATGCTGC 41*01 AACATATTACTGTCAGCAGGGCAATAAGCACCCT SEQ ID NO: 709 IGKV7-3*01 TGGAATCCCACCTCGATTCAGTGGCAGCGGGTATGGAACAGATTTTACCCTCACAATTAATAACATAGAATCTGAGGATGCTGCATA TTACTTCTGTCTACAACATGATAATTTCCCTCT SEQ ID NO: 710 IGLV(I)- GTCCCTGATGGCTTCTCTGGCTCCAAGTCTGGAAACACAGCCTCCATGACCATCTCTGGGTTCCAGGCTGAGGATGAGGCTGATTAT 20*01 TACTGCAACTCACATAGGAGAGGTGGCACTTTC SEQ ID NO: 711 IGLV(I)- TCCAGAACTGATTCTTGAGTGATCAGTCTGGCAAGGAGGCCTTCCTGAGCATATCTGGGCTCCAGGCTGAGGACAAGGCTGATCAC 38*01 TAACGTTGGATTTGGACAGTTCTCTGGAGGCCCC SEQ ID NO: 712 IGLV(I)- TTCAGGACAGACGCTCAGGCTACCAGTCTTGCATGAAGCCCTTCCTAAGCATCTCTGGGCTTTAGGCTGAGGACAAGGCTGATCACT 42*01 CCTGTTGGCTTCAGACAGCCCCCTGGAGGTCCA SEQ ID NO: 713 IGLV(I)- CCTCAGGGAATTTCCCAGCCCCATGTTAGGCAGTTTGGCCTCCCTGGCCATCTCTGGGCTCCAGGCTGGCGACGGTGCTGATTTTCA 56*01 CTATTTAGCACAGAATGGCAGCCTCGCTGATTA SEQ ID NO: 714 IGLV(I)- TCCCTGACAATTCTCTGGCTTCAAGTCTGGCAACTCCATTTTCGTGACCATCACTGTGCTACAGCCTGAAGATGAGGCTGATTATCAC 63*01 TGCCAATTCTACAAAAACAGCCTGAGTGCTTT SEQ ID NO: 715 IGLV(I)- CATAGGCCCAATGCTGAGGCTCCAGGTTGGAGAACATGGCCTCTCTGAGCATCTCTGGACTCCAGGCAGAGGAAAAGGCTGATTTT 68*01 TATTCTCAGCTTGGGACACAAGCACCAAGGCTCA SEQ ID NO: 716 IGLV(I)- CCCTGACCGCTTCTCTGGCTCAAAGTCTGGGACCACAGCCTCCCTGACTATCTCGGGCCTCTAGCCTGAGGACGAGGCTGATTATTA 70*01 CTGTTCAACATGGGACTACAGCCTCAGTGCTCA SEQ ID NO: 717 IGLV(IV)- CAGACAATTCTCTGGGTTGAGAGGCTCCTCCAGAGTCTCAAGTTATTTGGTCGTCTCTGGCCTTCACCTTGAGGATGGAGCAGATCA 53*01 TCTCTCTCAGATGGGCTGACAGGGCATGGCTTA SEQ ID NO: 718 IGLV(IV)- CTAAATCCAAAGATGCCTTGGCCAGTGCAGGCAATTTGCTCATCTCTGGGGTCCAGCCAGAGGACAAGACTATCTGTTCTATCTATT 59*01 ACTGTCAGACCTGGGATATTGATACTTCAGTTA SEQ ID NO: 719 IGLV(IV)- TCTGGATTAATGGAAGGCCGGTCCATAAAGGGCTCTTGCTCATATCTGATCTCCAGTCTGAGGATGAGGCTTACTATTACTGTATG 64*01 ATCGAGCACAGCAGAGCTTCTCATGCTGACACA SEQ ID NO: 720 IGLV(IV)- GTTCCCATCCACTTCTCTGGATCCAATGATACATTAGCCAATGCAGGGATTCTGTACATTCCTGGGCTGAAGCCTGAGGGTGAGGCT 65*01 ATTACTGTTGTACGTGTCACAGCAGCTCCAAGT SEQ ID NO: 721 IGLV(IV)-66- GTCACTTCTGTGAATCCAAAGATCCCTCGGGCAATGTGCAGGGATTCTGCACATTTCTGAGCAGCCTGAGATCAAGTCCGACTATTA 1*01 CTATTTTACATATCACAGCAACAGTGGCACTTT SEQ ID NO: 722 IGLV(V)- TACAGTTCTCAGGATCCAGCTATGGGGCTGATCGGTAGGTCACCATCTCCAACATCCAGTTTGAGGATGAAGCTGATTGTATCTGTG 58*01 GTGCAGATCATAGCATTGGTGTACATATGGGT SEQ ID NO: 723 IGLV(V)- ATTCCCAGTCACTAGTTCTCAGTCTCCAGGACTGGAGCTGACCACTATAGTGTCATTTCTACAATCCCGTCTGAGGATGGAGCTGACT 66*01 ATATCTGTGGTACAGATTGTAGCATTGGTGTG SEQ ID NO: 724 IGLV(VI)-22- AGAGACATAAGACTCATTCTCAGGCTCCAAGTCTGGCCAGTGAGCTTCTTTGAGACTCCCTGGGATCCCAGCAGTGACACTGATCAC 1*01 TATTGCTGTCCCACACATCCCAAGTGATGAGGA SEQ ID NO: 725 IGLV(VI)-25- AGAGACATAAGATTGATTCTCAGGCTCCAAGTCTGACAAGTGAGCTTCTTTGAGACTCCCTGGGATCCCAGCAGTGACACTGATCAC 1*01 TGTTGCTGTTCCACACATCCCAAGTGATGAGGA SEQ ID NO: 726 IGLV10- CTCAGAGAGATTATCTGCATCCATATCAGGAAACACAGCCTCCCTGACCATTACTGGACTCCAGCCTGAGGACGAGGCTGACTATTA 54*01 CTGCTCAGCATGGGACAGCAGCCTCAGTGCTCA SEQ ID NO: 727 IGLV10- ATCTCAGAGAGAATCTCTGCATCCAGGTCAGGAAACACAGCCTCCCTGACCATTACTGGACTCCAGCCTGAGGACGAGGCTGACTA 54*02 TTACTGCTCAGCATGGGACAGCAGCCTCAGTGCT SEQ ID NO: 728 IGLV10- AAAGAAAAAGGAGATATTCCTGAGGGGTACAGTGTCTCTAGAGAGAAGAAGGAGCGCTTCTCCCTGATTCTGGAGTCCGCCAGCA 54*03 CCAACCAGACATCTATGTACCTCTGTGCCAGCAGC SEQ ID NO: 729 IGLV10- GCTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCATCTCTGGGCTTCAGGCTGAGAACGAGGCTGATTATT 67*01 ACTGCAGTTCATATACAAGCACCACCACTCTC SEQ ID NO: 730 IGLV10- TCTCAGAGAGATTCCCTGGCTCCCGGTTAGGAACATGGCATCTCTGACCATCTCTGGCCTCCAGACCAAGGACAAGCCTGCCTATTA 67*02 CTGCTCAGCCTGGGACAGCAGCCTCAGTGCTCA SEQ ID NO: 731 IGLV110 CCCAGTCGAGTCTCTGGCTCCAAGGAGACCTCAAGTAACACAGCGTTTTTGCTCATCTCTGGGCTCCAGCCTGAGGACGAGGCCGAT 55*01_IGLV11- TATTACTGCCAGGTGTACGAAAGTAGTGCTAAT 1-55*02 SEQ ID NO: 732 IGLV1-36*01 CTCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGGCTGATTATTA CTGTGCAGCATGGGATGACAGCCTGAATGGTCC SEQ ID NO: 733 IGLV1-40*01 CCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCACTGGACTCCAGGCTGAGGATGAGGCTGATTATTA CTGCCAGTCCTATGACAGCAGCCTGAGTGGTTC SEQ ID NO: 734 IGLV1-40*02 GTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCACTGGGCTCCAGGCTGAGGATGAGGCTGATTAT TACTGCCAGTCCTATGACAGCAGCCTGAGTGGT SEQ ID NO: 735 IGLV1-40*03 GTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCGCCTCAGCCTCCCTGGCCATCACTGGGCTCCAGGCTGAGGATGAGGCTGATTAT TACTGCCAGTCCTATGACAGCAGCCTGAGTGGT SEQ ID NO: 736 IGLV1-41*01 ATTCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGCCACCCTGGGCATCACTGGCCTCTGGCCTGAGGACGAGGCCGATTAT TACTGCTTAGCATGGGATACCAGCCCGAGAGCT SEQ ID NO: 737 IGLV1-41*02 TCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGCCACCCTGGGCATCACTGGCCTCTGGCCTGAGGACTAGGCCGATTATTA CTGCTTAGCATGGGATACCAGCCTGAGAGCTTG SEQ ID NO: 738 IGLV1-44*01 CCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGGCTGATTATTA CTGTGCAGCATGGGATGACAGCCTGAATGGTCC SEQ ID NO: 739 IGLV1-44-01 GTCCCTGCCCGATTCTCTGGCTCCAGGTCTGGCACCTCAGCCTCCCTGGCCATCCGTGGGCTCCAGTCTGACGATGAGGGTGATTAT TTCTGTTCGGCATGGGATGACAGCCTGAATCAT SEQ ID NO: 740 IGLV1-47*01 GGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCGGTCCGAAGATGAGGCTGTTT ATTACTGTGGAGCGTGGGATGGCGGCCTGAGTG SEQ ID NO: 741 IGLV1-47*02 CCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCGGTCCGAGGATGAGGCTGATTATTA CTGTGCAGCATGGGATGACAGCCTGAGTGGTCC SEQ ID NO: 742 IGLV1-50*01 CCCTGACCATTCTCTGGCTCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCACTGGACTCCAGTCTGAGGATGAGGCTGATTATTAC TGCAAAGCATGGGATAACAGCCTGAATGCTCA SEQ ID NO: 743 IGLV1-51*01 ATTCCTGACCGATTCTCTGGCTCCAAGTCGGCACGTCAGCCACCCTGGGCATCACCGGACTCCAGACTGGGGACGAGGCCGATTAT TACTGCGGAACATGGGATAGCAGCCTGAGTGCT SEQ ID NO: 744 IGLV1-51*02 TCCTGACCGATTCTCTGGCTCCAAGTCTGGCACGTCTGCCACCCTGGGCATCACCGGACTCCAGACTGGGGACGAGGCCGATTATTAz TTGCGGAACATGGGATAACAATCTGCGTGCGGG SEQ ID NO: 745 IGLV1-62*01 TATCTGACCAATTCTCTGGTTCCAAGTCTGGCAGCTTGGCCTCCCTGGGCACCACTGGGCTCTGGGCTGAGGACAAGACTGATTATC ACTGCCAGTCCCGTGACATCTGCTGAGTGCTTG SEQ ID NO: 746 IGLV2-11*01 GGGTCCCTGATCGTCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCATCTCTGGGCTCCAGGCTGAGGATGAGGCTGATT ATTACTGCTGCTCATATGCAGGCAGCTACACTT SEQ ID NO: 747 IGLV2-11*02 GTCCCTGATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCATCTCTGGGCTCCAGGCTGAGGATGAGGCTGATTAT TACTGCTGCTCATATGCAGGCAGCTACACTTTC SEQ ID NO: 748 IGLV2-14*01 GTCTCTAATCGCTTCTCTGGTTCCAAGTCTGGCAACACGGCCTCCCTGACCAATCTCTGGGCTCCAGGCTGAGGACGAGGCTGATTAT TACTGCAACTCATATCAACCAGCGACACTCTC SEQ ID NO: 749 IGLV2-14*02 GTTTCTAATCGCTTCTCTGGCTCCAAGTCTGCCAACACGGCCTCCCTGACAATCTCTGGGCTCCAGGCTGAGGACGAGGCTGATTATT ACTGCAGCTCATATACAAGCAGCAGCACTCTC SEQ ID NO: 750 IGLV2-18*01 AAGTACGCGGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAGGAACACGCTGTATCTGCAGATGAACAGTCTGAG AGCCGAGGACACGGCTGTGTATTATTGTGCAAGA SEQ ID NO: 751 IGLV2-18*02 TCTTGGACCCCTGCCCGGTTCTCAGGCTCCCTCCTCGGGGGCAAAGCTGTCCTGACACTGTCAGGTGTGCAGCCTGAGGACGAGGC TGAGTATTACTGCATGCTCTACTCTAGTGGTCCT SEQ ID NO: 752 IGLV2-18*03 GTCCCTGATCGCTTCTCTGGGTCCAAGTCTGGCAACACGGCCTCCCTGACCACCTCTGGGCTCCAGGCTGAGGACGAGGCTGATTAT TACTGCAGCTCATATACAAGCAGCAGCACTTTC SEQ ID NO: 753 IGLV2-18*04 GTCCCTGATCGCTCCTCTGGGTCCAAGTCCGGCAACACGGCCTCCTGACCATCTCTGGGCTCCAGGCTGAGGACGAGGCTGATTAT TACTGCAGCTCATATACAAGCAGCAGCACTTTC SEQ ID NO: 754 IGLV2-23*01 TTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACAATCTCTGGGCTCCAGGCTGAGGACGAGGCTGATTATT ACTGCTGCTCATATGCAGGTAGTAGCACTTTAC SEQ ID NO: 755 IGLV2-23*02 GTTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACAATCTCTGGGCTCCAGGCTGAGGACGAGGCTGATTAT TACTGCTGCTCATATGCAGGTAGTAGCACTTTC SEQ ID NO: 756 IGLV2-23*03 GGGTTTCTGATCGCTTCTCTGGCTCCAAGTCTGGCAGCACGGCCTCCCTGACAATTTCTGGGCTCCAGGCTGAGGATGAGGCTGATT ATTACTGCTGCTCATATGTTGGCAGTCACACTT SEQ ID NO: 757 IGLV2-28*01 TCTCTGATCACTTCTCTGGCTCCCAGCTCTGGCAACATGGCCTCCATGACCATCTCTGGGCTTCCAGGCTGAGGACGAGGCTGATTATT ACTGCAGTTCATATACAAGCAGCAACATTTTC SEQ ID NO: 758 IGLV2- ATCTCTGACCTCTTCTCAGGCTCCAAGTCTGGCAACATGGCTTCCCTGACCATCTCTGGGCTCAAGTCCGAGGTTGAGGCTAATTATC 33*01_IGLV2- ACTGCAGCTTATATTCAAGTAGTTACACTTTC 33*02 SEQ ID NO: 759 IGLV2-33*03 ATCTCTGACCTCTTCTCAGGCTCCAAGTCTGGCAACGTGGCTTCCCTGACCATCTCTGGGCTCAAGTCCGAGGTTGAGGCTAATTATC ACTGCAGCTTATATTCAAGTAGTTACACTTTC SEQ ID NO: 760 IGLV2- GCCCCTGGTTGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCATCTCTGGGCTCCAGGCTGAGGACGAGGCTGATTAT 34*01_IGLV2- TACTGCAGCTCATATGCAGGCAGCTACAATTTC NL1*01 SEQ ID NO: 761 IGLV2-5*01 GTCCCTGATCGTTTCTCTGGCTCCAAGTCTGGCAATACGGCCTCCATGACCATCTCTGGACTCCAGGCTGAGGACGAGGCTGATTAT TAGTGCTGCTCATATACAAGCAGTGCCACTTAA SEQ ID NO: 762 IGLV2-5*02 TCCCTGATCGTTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCATGACCATCTCTGGACTCCAGGCTGAGGACGGCTGATTATT AGTGCTGCTCATATACAAGCAGTGCCACTTAAC SEQ ID NO: 763 IGLV2-8*01 GGTCCCTGATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCGTCTGTGGGCTCCAGGCTGAGGACGAGGCTGATTA TTACTGCAGCTCATATGCAGGCAGCAACAATTT SEQ ID NO: 764 IGLV2-8*02 GTCCCTGATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCGTCTCTGGGCTCCAGGCTGAGGATGAGGCTGATTAT TACTGCAGCTCATATGCAGGCAGCAACAATTTC SEQ ID NO: 765 IGLV3-1*01 AGGGATCCCTGAGCGAATCTCTGGCTCCAAGTCTGGGAACACAGCCACTCTGACCATCAGCGGGACCCAGGCTATGGATGAGGCTG ACTATTACTGTCAGGCGTGGGACAGCAGGGCTGC SEQ ID NO: 766 IGLV3-10*01 CCCTGAGAGATTCTCTGGCTCCAGCTCAGGGACAATGGCCACCTTGACTATCAGTGGGGCCCAGGTGGAGGATGAAGCTGACTACT ACTGTTACTCAACAGACAGCAGTGGTAATCATTG SEQ ID NO: 767 IGLV3-12*01 CCCTGAGCGATTCTCTGGCTCCAACCCAGGGAACACCACCACCCTAACCATCAGCAGGATCGAGGCTGGGGATGAGGCTGACTATT ACTGTCAGGTGTGGGACAGTAGTAGTGATCCCCC SEQ ID NO: 768 IGLV3-12*02 CCCTGAGCGATTCTCTGGCTCCAACCCAGGGAACACCGCCACCCTAACCATCAGCAGGATCGAGGCTGGGGATGAGGCTGACTATT ACTGTCAGGTGTGGGACAGTAGTAGTGATCATCC SEQ ID NO: 769 IGLV3-13*01 TGGAATCCCTGAGCGATTCTCTGGGTCCACCTCAGGGAACACAACCGCCCTGACCATTAGCAGGGTCCTGACCAAAGGCGGGGCTG ACTATTACTGTTTTTCTGGTGATTAGAACAATCT SEQ ID NO: 770 IGLV3-15*01 GGATCTCTGAGAGATTCTCTGGCTCCAACTTGGGGAACGTGGCCACCCTGACCATCAACAGGACCCAGGGTGGGGACAAGGCTATT ACTGTAAGATGTGGGACATTAGCACTCCTCATCC SEQ ID NO: 771 IGLV3-16*01 ATCCCTGAGCGATTCTCTGGCTCCAGCTCAGGGACAATAGTCACATTGACCATCAGTGGAGTCCAGGCAGAAGACGAGGCTGACTA TTACTGTCTATCAGCAGACAGCAGTGGTACTTAT SEQ ID NO: 772 IGLV3-17*01 TCCCAGACCGATTCTCTGGCTCCAAGTCAGGAACACAGCCACCCTGACCATCACTGGGGCTCAGGTTGAACATGAAGCTGACTATTA CCGTCACTCATGGGACAACAGTGGTACTCATCT SEQ ID NO: 773 IGLV3-19*01 CGGGCCTCCGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACACTGAAAATCAGCAGAGTGGAGGCTGAGG ATGTTGGGGTTTATTACTGCATGCAAGCTCTACAT SEQ ID NO: 774 IGLV3-2*01 AGTGATTCCTGAGCAATTTTCTGACTGCATATCAGAGGACATGGCCACCTTGATTATTAATGGGGCACAGGATGGAAACAAGGCTA TTACTGTCGCTCGGAACAGCACTGCTTCTCATCT SEQ ID NO: 775 IGLV3-21*01 GGATCCCTGACCGATTCTCTGGCTCCAATTCTGGGAACACGGCCACCCCGACCATCAGCAGGGTCGAAGCCGGGGATGAGGCCGAC TATTACTGTCAGGTGTGGGATGTGAATAGTGATC SEQ ID NO: 776 IGLV3-21*02 ATCCCTGAGCGATTCTCTGGCTCCAACTCTGGGAACACGGCCACCCTGACCATCAGCAGGGTCGAAGCCGGGGATGAGGCCGACTA TTACTGTCAGGTGTGGGATAGTAGTAGTGATCAT SEQ ID NO: 777 IGLV3-21*03 CCCTGAGCGTTTCTCTGGCTCCAACTCTGGGAACACGGCCACCCTGACCATCAGCAGGGTCGAAGCCGGGGATGAGGCCGACTATT ACTGTCAGGTGTGGGAGAGTAGTAGTGAACCACC SEQ ID NO: 778 IGLV3-22*01 TGGAATCCCTGAACGATTCTCTGGGTCCACCTCAGGGAACACGACCACCCTGACCATCAGCAGGGTCCTGACCGAAGACGAGGCTG ACTATTACTGTTTGTCTGGGGATGAGGACAATCC SEQ ID NO: 779 IGLV3-22*02 TGGAATCCCTGAACGATTCTCTGGGTCCACCTCAGGGAACACGACCACCCTGACCATCAGCAGGGTCCTGACCGAAGACGAGGCTG ACTATTACTGTTTGTCTGGGAATGAGGATAATCC SEQ ID NO: 780 IGLV3-24*01 CAGGGATCTCTGAGATTCTCTGGCTCAAACTCAGGGAACAGGACCACCCTGGCCATCAACAGGGCCCAGGCTGGGACGAGGCTATT ACTGTAAGATGTGGGACATTAGGACTCCTCATCC SEQ ID NO: 781 IGLV3-24*02 AGGGATCTCTGAGATTCTCTGGCTCAAACTCAGGGAACAGGACCACCCTGGCCATCAACAGGGCCCAGGCTGGGGACCAGGCTATT ACTGTAAGATGTGGGACATTAGGACTCCTCATCC SEQ ID NO: 782 IGLV3-25*01 CCCTGAGCGATTCTCTGGCTCCAGCTCAGGGACAACAGTCACGTTGACCATCAGTGGAGTCCAGGCAGAAGATGAGGCTGACTATT ACTGTCAATCAGCAGACAGCAGTGGTACTTATCC SEQ ID NO: 783 IGLV3-25*02 GCGACAATATATCGTGCGTCGGTGAAAGGCAGATTCACCATCTCCAGAGATGATTCAAAAACATGGCGTTTCTGCAAATGGACAG CCTGAGACCCGACGACACGGCCCTGTATTACTGT SEQ ID NO: 784 IGLV3-25*03 CTCAGGGATCCCTGAGCGATTCTATGGCTCCACCTCAGGGACAACAGTCACGTTGACCATCAGTGGAGTCCAGGCAGAAGACGAGG CTGACTATTACTGTCAATCAATTGACAAAAGTGG SEQ ID NO: 785 IGLV3-26*01 TCCCAGACCAATTCTCTGGCTCCAAGTCAGGAACACAGCCACCCTGACCATCACTGGGGCTCAGGTTGAACATGAAGCTGACTATTA CCATCACTCATGGGACAGCAGTGCTACTCACCT SEQ ID NO: 786 IGLV3-27*01 AGGGATCCCTGAGCGATTCTCCGGCTCCAGCTCAGGGACCACAGTCACCTTGACCATCAGCGGGGCCCAGGTTGAGGATGAGGCT GACTATTACTGTTACTCTGCGGCTGACAACAATCT SEQ ID NO: 787 IGLV3-29*01 CTTCAGGGATCTCTAAGTGATTCTCCAGCTCCAACTCGGGGAACATGGTCACCCTGACCATCAGTGGAGCCCAGGCTGGGGACGAG GCTTTCCTCTCAGGTGTGGGGCAGTGGCACTGCA SEQ ID NO: 788 IGLV3-30*01 AGTGATTCTCTGGCTCCAACTTGTGGAACACAGCCACTCTGACCATTAGTGGGGCCCAGGCCAGGGACGAGGCTATTACTGTAGCA CCTATGATGGCTGAGGGAGCAGCAGCCAGTGGCT SEQ ID NO: 789 IGLV3-30*02 AGTGATTCTCTGGCTCCAACTTGTGGAACACAGCCACTCTGACCATTAGTGGGGCCCAGGCCAGGGACGAGGCTATTACTGTAGCA CCTATGATGGCTGAGGGAGCAGCAGGCAGTGGCT SEQ ID NO: 790 IGLV3- TCCTAAGAAATTCTCTGGCTCCAGCTCAGGGAACATGGCCACCCTGACCATCACTGGGATTCAGGTTGAAGACAAGGCTGACTATTA 31*01_IGLV3- CTGTCAGTCATGGGACAGCAGTCGTACTCATTC 31*02 SEQ ID NO: 791 IGLV3-32*01 AAGGATCCCTGAGCGATTCTCTGGCTCCAAATCAGGCAACACAACCACCCTGACCATCACTGGGGCCCAGGCTGAGGATGAGGCTG ATTATTACTATCAGTTGATAGACAACCATGCTAC SEQ ID NO: 792 IGLV3-4*01 GCTCAGAGATCACTGAGCGATTCTCTGGTTCCTGCTCAGGGGGAACAGCCACACTGACCATTACTGGGGCTCACGTTGAAGACGAG GCTATTTTTGTTTTTCTGGAGATAAAAACACATT SEQ ID NO: 793 IGLV3-6*01 GAATTTCTGATTTTCTGAGTCCAGCTCAGGGAACATGGCCACCCTGACCATCAGCAGGGCTCAGACTGAGGACGAGGCTGACTATT ACTGTCACAGGTACAATAGAAACAGTGATGAGCC SEQ ID NO: 794 IGLV3-6*02 GAATTTCTGATTTTCTGAGTCCAGCTCAGGGAACATGGCCACCCTGACCATCATCAGGGCTCAGACTGAGGACGAGGCTGACTATTA CTGTCACAGGTACAACAGAAACAGTGATGAGCC SEQ ID NO: 795 IGLV3-7*01 TGATTCCTGAACAACTCTCTGACTCCATATCAGAGAACATGGCCACCCTGATAATCAATGGGCCCCAGGCTGGAAACAAGGCTATTA CTGTCAATCATGAGACAGCACTGATACTCATCT SEQ ID NO: 796 IGLV3- GGGATCCCTGAGCGATTCTCTGGCTCCAACTCGGGGAACACGGCCACCCTGACCATCAGCAGAGCCCAAGCCGGGGATGAGGCTG 9*01_IGLV3- ACTATTACTGTCAGGTGTGGGACAGCAGCACTGCA 9*03 SEQ ID NO: 797 IGLV3-9*02 CCCTGAGCGATTCTCTGGCTCCAACTCGGGGAACACGGCCACCCTGACCATCAGCAGAGCCCAAGCCGGGGATGAGGCTGACTATT ACTGTCAGGTGTGGGACAGCAGCACTGCACACCC SEQ ID NO: 798 IGLV4-3*01 TACTACGCAGACTCAGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGAG AGCCGAGGACACGGCTGTGTATTACTGTGCGAGA SEQ ID NO: 799 IGLV4-60*01 AGCGGAGTTCCTGATCGCTTCTCAGGCTCCAGCTCTGGGGCTGACCGCTACCTCACCATCTCCAACCTCCAGTTAGAGGATGAGGCT GATTATTACTGTGAGACCTGGGACAGTAACACT SEQ ID NO: 800 IGLV4-60*02 GGAGCGGAGTTCCTGATCGCTTCTCAGGCTCCAGCTCTGGGGCTGACCGCTACCTCACCATCTCCAACCTCCAGTTTGAGGATGAGG GTGATTATTACTGTGAGACCTGGGACACTAACA SEQ ID NO: 801 IGLV4-60*03 GGCGGAGATCCGAATCGCTTCTCAGGCTCCAGCTCTGGGGCTGACCGCTACCTCACCATCTCCAACCTCCAGTCTGACGATCAGGCT GATTATTACTGTGAGACCTGGGACAGTGACACT SEQ ID NO: 802 IGLV4-69*01 GAGACGGGATCCCTGATCGCTTCTCAGGCTCCAGTTCTGGGGCTGAGCGCTACCTCACCATCTCCAGCCTCCAGTCTGAAGATGAGG CTGAGTATTACTGTCAGACCTGGGGCCCTGGCA SEQ ID NO: 803 IGLV4-69*02 GGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAACTT ACTACTGTCAACAGAGTTACAGTACCCCTGGAT SEQ ID NO: 804 IGLV5-37*01 CCCAGCCGCTTCTCTGGATCCAAAGATGCTTCAGCCAATACAGGGATTTTACTCATCTCCGGGCTCCAGTCTGAGGATGAGGCTGAC TATTACTGTATGATTTGGCCAAGCCAATGCTTCT SEQ ID NO: 805 IGLV5-39*01 TCCCCAGCCGCTTCTCTGGATCCAAAGATGTTTCAACCAATGCAGGCCTGTTACTCATCTCTGGGCTCCAGTCTGAAGATGAGGCTG ACTATTACTGTGCCATTTGGTACAGCAGCTCTT SEQ ID NO: 806 IGLV5-39*02 CCCAGCCGCTTCTCTGGATCCAAAGATGCTTCAACCAATGCAGGCCTTTTACTCATCTCTGGGCTCCAGTCTGAAGATGAGGCTGACT ATTACTGTGCCATTTGGTACAGCAGCACTTCT SEQ ID NO: 807 IGLV5-45*01 CTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCA GTGTATTACTGTCAGCAGTATGGTGACTCACCTC SEQ ID NO: 808 IGLV5-45*02 TCCCCAGCCGCTTCTCTGGATCCAAAGATGCTTCGGCCAATGCAGGGATTTTACTCATCTCTGGGCTCCAGTCTGAGGATGAGGCTG ACTATTACTGTATGATTTGGCACAGCAGCGCTT SEQ ID NO: 809 IGLV5-45*03 AGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATAAGCAGTCTGCAACCTGAAGATTTTGC AACTTACTACTGTCAACAGACTTATCGAAGCCGG SEQ ID NO: 810 IGLV5-45*04 CCCAGCCGCTTCTCTGGATCCAAAGATGCTTCGGCCAATGCAGGGATTTTACTCATCTCTGGGCTCCAGTCTGAGGATGAGGCTGAC TATTACTGTATGATTTGGCACAGCAGCGCTTCT SEQ ID NO: 811 IGLV5-48*01 CCCAGCCGCTTCTCTGGATCCAAAGATGCTTCGAGCAATGCAGGGATTTTAGTCATCTCTGGGCTCCAGTCTGAGGATGAGGCTGAC TATTACTGTATGATTTGGCACAGCAGTGCTTCT SEQ ID NO: 812 IGLV5-48*02 CCCAGCCGCTTCTCTGGATCCAAAGATGCTTCGACCAATGCAGGGATTTTATTCATCTCTGGGCTCTAGTCTGAGGATGAGGCTGAC TATTACTGTATGATTTGGCACAGCAGTGCTTCT SEQ ID NO: 813 IGLV5-52*01 CGCTTCTCTGGATCCAACGATGCATCAGCCAATGCAGGGATTCTGCGTATCTCTGGGCTCCAGCCTGAGGATGAGGCTGACTATTAC TGTGGTACATGGCACAGCAACTCTAAGACCCCT SEQ ID NO: 814 IGLV6- CCCTGATCGGTTCTCGGCTCCATCGACAGCTCCTCCAACTCTGCCTCCCTCACCATCTCTGGACTGAAGACTGAGGACGAGGCTGAC 57*01_IGLV6- TACTACTGTCAGTCTTATGATAGCAGCAATCA 57*02 SEQ ID NO: 815 IGLV7-35*01 GGACCCCTGCCCAGTTCTCAGGCTCAGTCCTTGGGAGCAAAGCTGCCCAGACACTCTTGGGTGTGCAGCCCGAGAGGTGAAGCTGA GTACTACTGCTTACTGCACCATAGTCGTGCTTGG SEQ ID NO: 816 IGLV7-43801 TGGACCCCTGCCCGGTTCTCAGGCTCCCTCCTTGGGGGCAAAGCTGCCCTGACACTGTCAGGTGTGCAGCCTGAGGACGAGGCTGA GTATTACTGCCTGCTCTACTATGGTGGTGCTCAG SEQ ID NO: 817 IGLV7-46*02 TGGACACCTGCCCGGTTCTCAGGCTCCCTCCTTGGGGGCAAAGCTGCCCTGACCCTTTTGGGTGCGCAGCCTGAGGATGAGGCTGA GTATTACTGCTTGCTCCTATAGTGGTGCTCGG SEQ ID NO: 818 IGLV7-46*03 CTGGACACCTGCCCGGTTCTCAGGCTCCCTCCTTGGGGGCAAAGCTGCCCTGACCTTTTCGGGTGCGCAGCCTGAGGATGAGGCTGA GTATTACTGCTTGCTCTCCTATAGTGGTGCTCGG SEQ ID NO: 819 IGLV8/OR8- CCTGGTCGCTTCTCTGGCTCCATCCTTGGGAACAAAGCTGCCCTCACCATCACGGGGACTCAGTAGATGATGACTCTGATCATTACT 1*01 GTGTGCTGTACATGGGTAGTGGCAATTCCACAG SEQ ID NO: 820 IGLV8/OR8- GGGGTCCCTGGTCGCTTCTCTGGCTCCATCCTTGGGAACAAAGCTGCCCTCACCATCACGGGGACTCAGGTAGATGATGACTCTGAT 1*02 CATTACTGTGTGCTGTACATGGGTAGTGGCAAT SEQ ID NO: 821 IGLV8-61*01 CTTCTGGGGTCCCTGATCGCTTCTCTGGCTCCATCCTTGGGAACAAAGCTGCCCTCACCATCACGGGGGCCCAGGCAGATGATGAAT CTGATTATTACTGTGTGCTGTATATGGGTGGTG SEQ ID NO: 822 IGLV8-61*02 GGTCCCTGATTGCTTCTCTGGCTCCATCCTTGGGAACAAAGCTGCCCTCACCATCACGGGGGCCCAGGCAGATGATGAATCTGATTA TTACTGTGTGCTGTATATGGGTAGTGGCATTTC SEQ ID NO: 823 IGLV9-49*01 TGATCGCTTCTCAGTCTTGGGCTCAGGCCTGAATCGGTACCTGACCATCGAGAACATCCAGGAAGAGGATGACAGTGACTTCCACT GTGGGGCAGACCATGGCAGTGGGAGCAACTTCGT SEQ ID NO: 824 IGLV9-49*02 CTTCTCAGTCTTGGGCTCAGGCCTGAATCGGTACCTGACCATCAAGAACATCCAGGAAGAAGATGAGAGTGACTACCACTGTGGGG CAGACCATGGCAGTGGGAGCAACTTCGTGTAACC SEQ ID NO: 825 IGLV9-49*03 CTTCTCAGTCTTGGGCTCAGGCCTGAATCGGTACCTGACCATCAAGAACATCCAGGAAGAGGATGAGAGTGACTACCACTGTGGGG CAGACCATGGCAGTGGGAGCAACTTCGTGTAACC SEQ ID NO: 826 VPREB1*01 TCCAAAGATGTGGCCAGGAACAGGGGGTATTTGAGCATCTCTGAGCTGCAGCCTGAGGACGAGGCTATGTATTACTGTGCTATGG GGGCCCGCAGCTCGGAGAAGGAGGAGAGGGAGAGG

TABLE B2 SEQ ID NO Name Sequence SEQ ID NO: 827  89161040 89161073 IGKJxxx-211891 TACACTTTTGGCCAGGGGACCAAGCTGGAAATCAG ACGTAAGTACTTTTTTCCACTGATTCTTCACTGTT GCTAATTAGTTTACTTTGTGTTCCTTTGTGTGGAT TTTCATTAGTCGG SEQ ID NO: 828  89160080 89160117 IGKJ5*01-X67858 GATCACCTTCGGCCAAGGGACACGACTGGAGATTA AACGTAAGTAATTTTTCACTATTGTCTTCTGAAAT TTGGGTCTGATGGCCAGTATTGACTTTTAGAGGCT TAAATAGGAGTTTGG SEQ ID NO: 829  2  89160398 89160435 IGKJ5*01-X67858 GCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCA AACGTAAGTGCACTTTCCTAATGCTTTTTCTTATA AGGTTTTAAATTTGGAGCGTTTTTGTGTTTGAGAT ATTAGCTCAGGTCAA SEQ ID NO: 830  2  89160733 89160770 IGKJ3*01-X67858 ATTCACTTTCGGCCCTGGGACCAAAGTGGATATCA AACGTAAGTACATCTGTCTCAATTATTCGTGAGAT TTTAGTGCCATTGTATCATTTGTGCAAGTTTTGTG ATATTTTGGTTGAAT SEQ ID NO: 831  2  89161037 89161075 IGKJ2*01-X67858 TGTACACTTTTGGCCAGGGGACCAAGCTGGAGATC AAACGTAAGTACTTTTTTCCACTGATTCTTCACTG TTGCTAATTAGTTTACTTTGTGTTCCTTTGTGTGG ATTTTCATTAGTCGG SEQ ID NO: 832  2  89161398 89161435 IGKJ1*01-X67858 GTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCA AACGTGAGTAGAATTTAAACTTTGCTTCCTCAGTT GTCTGTGTCTTCTGTTCCCTGTGTCTATGAAGTGA TCTATAAGGTGACTC SEQ ID NO: 833  2  89161398 89161433 IGKJ1*01-X63370 GGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAA CGTGAGTAGAATTTAAACTTTGCTTCCTCAGTTGT CTGTGTCTTCTGTTCCCTGTGTCTATGAAGTGATC TATAAGGTGACTCTG SEQ ID NO: 834  2  23235961 23235998 IGLJ1*01-X51755 GGCTCCTGCTCCAGCCCAGCCCCCAGAGAGCAGAC CCCAGGTGCTGGCCCCGGGGGTTTTGGTCTGAGCC TCAGTCACTGTGTTATGTCTTCGGAACTGGGACCA AGGTCACCGTCCTAG SEQ ID NO: 835  2  23235961 23235998 IGLJ1*01-X51755 TTATGTCTTCGGAACTGGGACCAAGGTCACCGTCC (2) TAGGTAAGTGGCTCTCAACCTTTCCCAGCCTGTCT CACCCTCTGCTGTCCCTGGAAAATCTGTTTTCTCT CTCTGGGGCTTCCTC SEQ ID NO: 836 22  23241798 23241835 IGLJ2*01-X51755 CAGCTTCCTCCTTCACAGCTGCAGTGGGGGCTGGG GCTGGGGCATCCCAGGGAGGGTTTTTGTATGAGCC TGTGTCACAGTGTGTGGTATTCGGCGGAGGGACCA AGCTGACCGTCCTAG SEQ ID NO: 837 22  23241798 23241835 IGLJ2*01-X51755 TGTGGTATTCGGCGGAGGGACCAAGCTGACCGTCC (2) TAGGTGAGTCTCTTCTCCCCTCTCCTTCCCCACTC TTGGGACAATTTCTGCTGTTTTTGTTTGTTTCTGT ATCTTGTCTCAACTT SEQ ID NO: 838 22  23241801 23241835 IGLJ3*02-D87023 CAGCTTCCTCCTTCACAGCTGCAGTGGGGGCTGGG GCTGGGGCATCCCAGGGAGGGTTTTTGTATGAGCC TGTGTCACAGTGTTGGGTGTTCGGCGGAGGGACCA AGCTGACCGTCCTAG SEQ ID NO: 839 22  23241801 23241835 IGLJ3*02-D87023 TTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCC (2) TAGGTGAGTCTCTTCTCCCCTCTCCTTCCCCGCTC TTGGGACAATTTCTGCTGTTTTTGTTTGTTTCTGT ATCTTGTCTCAACTT SEQ ID NO: 840 22  23247168 23247205 IGLJ3*02-D87023 AGCTTCCTCCTTCACAGCTGCAGTGGGGGCTGGGG CTAGGGGCATCCCAGGGAGGGTTTTTGTATGAGCC TGTGTCACAGTGTTGGGTGTTCGGCGGAGGGACCA AGCTGACCGTCCTAG SEQ ID NO: 841 22  23247168 23247205 IGLJ3*02-D87023 TTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCC (2) TAGGTGAGTCTCTTCTCCCCTCTCCTTCCCCGCTC TTGGGACAATTTCTGCTGTTTTTGTTTGTTTCTGT ATCTTGTCTCAACTT SEQ ID NO: 842 22  23247171 23247205 IGLJ3*01-X51755 AGCTTCCTCCTTCACAGCTGCAGTGGGGGCTGGGG CTAGGGGCATCCCAGGGAGGGTTTTTGTATGAGCC TGTGTCACAGTGTGTGGTATTCGGCGGAGGGACCA AGCTGACCGTCCTAG SEQ ID NO: 843 22  23247171 23247205 IGLJ3*01-X51755 TGTGGTATTCGGCGGAGGGACCAAGCTGACCGTCC (2) TAGGTGAGTCTCTTCTCCCCTCTCCTTCCCCGCTC TTGGGACAATTTCTGCTGTTTTTGTTTGTTTCTGT ATCTTGTCTCAACTT SEQ ID NO: 844 22  23252740 23252777 IGLJ4*01-X51755 GTATTTGGTGGAGGAACCCAGCTGATCATTTTAGA TGAGTCTCTTCTTCCCTTTCTTTCCCTGCCAAGTT GGTGACAATTTTATTCTGATTTCGATCTTTGTCTG TGACTTGCCACAGCC SEQ ID NO: 845 22  23252740 23252777 IGLJ4*01-X51755 TTTTGTATTTGGTGGAGGAACCCAGCTGATCATTT (2) TAGATGAGTCTCTTCTTCCCTTTCTTTCCCTGCCA AGTTGGTGACAATTTTATTCTGATTTCGATCTTTG TCTGTGACTTGCCAC SEQ ID NO: 846 22  23256443 23256480 IGLJ5*02-D87017 CAGAGAGGGTTTTTGTATGAGCCTGTGTCACAGCA CTGGGTGTTTGGTGAGGGGACGGAGCTGACCGTCC TAGATGAGTCTTTTCCCCCTCCTTCCCTGGTCTCC CCAAGGTACTGGGAA SEQ ID NO: 847 22  23256443 23256480 IGLJ5*02-D87017 CTGGGTGTTTGGTGAGGGGACGGAGCTGACCGTCC (2) TAGGATGAGTCTTTTCCCCCTCCTTCCCTGGTCTC CCCAAGGTACTGGGAAATTTTCTGCTGCTTTTGTT CTTTTCTGTATCTTG SEQ ID NO: 848 22  23260336 23260373 IGLJ6*01-X58181 GGAGGGTTTGTGTGCAGGGTTATATCACAGTGTAA TGTGTTCGGCAGTGGCACCAAGGTGACCGTCCTCG GTGAGTCCCCTTTTCTATTCTTTTGGGTCTAGGGT GAGATCTGGGGAGAC SEQ ID NO: 849 22  23260336 23260373 IGLJ6*01-X58181 TAATGTGTTCGGCAGTGGCACCAAGGTGACCGTCC (2) TCGGTGAGTCCCCTTTTCTATTCTTTTGGGTCTAG GGTGAGATCTGGGGAGACTTTTCTGTCCTTTCTGT TCTCTCTAGGGTAGA SEQ ID NO: 850 22  23263570 23263607 IGLJ7*01-X57808 TCACTGTGTGCTGTGTTCGGAGGAGGCACCCAGCT GACCGTCCTCGGTAAGTCTCCCCGCTTCTCTCCTC TTTGAGATCCCAAGTTAAACACGGGGAGTTTTTCC CTTTCCTGTCTGTCG SEQ ID NO: 851 22  23263570 23263607 IGLJ7*01-X57808 TGCTGTGTTCGGAGGAGGCACCCAGCTGACCGTCC (2) TCGGTAAGTCTCCCCGCTTCTCTCCTCTTTGAGAT CCCAAGTTAAACACGGGGAGTTTTTCCCTTTCCTG TCTGTCGAAGGCTAA SEQ ID NO: 852 22  23263570 23263607 IGLJ7*02-D87017 TCACTGTGTGCTGTGTTCGGAGGAGGCACCCAGCT GACCGCCCTCGGTAAGTCTCCCCGCTTCTCTCCTC TTTGAGATCCCAAGTTAAACACGGGGAGTTTTTCC CTTTCCTGTCTGTCG SEQ ID NO: 853 22  23263570 23263607 IGLJ7*02-D87017 TGCTGTGTTCGGAGGAGGCACCCAGCTGACCGCCC (2) TCGGTAAGTCTCCCCGCTTCTCTCCTCTTTGAGAT CCCAAGTTAAACACGGGGAGTTTTTCCCTTTCCTG TCTGTCGAAGGCTAA SEQ ID NO: 854 22 106329408 1.06E+08 IGHJ6*03-M63030 TACTACTACTACTACTACATGGACGTCTGGGGCAA AGGGACCACGGTCACCGTCTCCTCAGGTAAGAATG GCCACTCTAGGGCCTTTGTTTTCTGCTACTGCCTG TGGGGTTTCCTGAGC SEQ ID NO: 855 22 106329408 1.06E+08 IGHJ6*03-M63030 ATTACTACTACTACTACTACATGGACGTCTGGGGC (2) AAAGGGACCACGGTCACCGTCTCCTCAGGTAAGAA TGGCCACTCTAGGGCCTTTGTTTTCTGCTACTGCC TGTGGGGAATTC SEQ ID NO: 856 14 106329408 1.06E+08 IGHJ6*04-AJ879487 ATTACTACTACTACTACGGTATGGACGTCTGGGGC AAAGGGACCACGGTCACCGTCTCCTCAGGTAAGAA TGGCCACTCTAGGGCCTTTGTTTTCTGCTACTGCC TGTGGGGTTTCCTGA SEQ ID NO: 857 14 106329409 1.06E+08 IGHJ6*03-X86359 TGATGCTTTTGATATCTGGGGCCAAGGGACAATGG TCACCGTCTCTTCAGGTAAGATGGCTTTCCTTCTG CCTCCTTTCTCTGGGCCCAGCGTCCTCTGTCCTGG AGCTGGGAGATAATG SEQ ID NO: 858 14 106329626 1.06E+08 IGHJ3P*02-X97051 CTTGCAGTTGGACTTCCCAGGCCGACAGTGGTCTG GCTTCTGAGGGGTCAGGCCAGAATGTGGGGTACGT GGGAGGCCAGCAGAGGGTTCCATGAGAAGGGCAGG ACAGGGCCACGGACA SEQ ID NO: 859 14 106330024 1.06E+08 IGHJ4-U42590 GACTATTGGGGCCAGGGAACCCTGGTCACCGTCTC CTCAGGTGAGTCCTCACAAGCTCTCTCCTACTTTA ACTCAGAAGACTCTCACTGCATTTTTGGGGGGAGA TAAGGGTGCTGGGTC SEQ ID NO: 860 14 106330024 1.06E+08 IGHJ4*02-X97051 ACTACTTTGACTACTGGGGCCAGGGAACCCTGGTC ACCGTCTCCTCAGGTGAGTCCTCACAACCTCTCTC CTGCTTTAACTCTGAAGGGTTTTGCTGCATTTTTG GGGGGAAATAAGGGT SEQ ID NO: 861 14 106330024 1.06E+08 IGHJ4-U42588 AACTGGTTCGACCCCTGGGGCCAGGGAACCCTGGT CACCGTCTCCTCAGGTGAGTCCTCACCACCCCCTC TCTGAGTCCACTTAGGGAGACTCAGCTTGCCAGGG TCTCAGGGTCAGAGT SEQ ID NO: 862 14 106330024 1.06E+08 IGHJ5-M18810 CAGTGCTTCGACCCCTGGGGCCAGGGAACCCTGGT CACCGTCTCCTCAGGAGATTCCTCACCACCCCCTC TCTGAGTCCTCTTAGTGAGACTCAGTTTGCCGGAC TCTCAGGGTCAGAGT SEQ ID NO: 863 14 106330024 1.06E+08 IGHJ5*02-X97051 ACAACTGGTTCGACCCCTGGGGCCAGGGAACCCTG GTCACCGTCTCCTCAGGTGAGTCCTCACCACCCCC TCTCTGAGTCCACTTAGGGAGACTCAGCTTGCCAG GGTCTCAGGGTCAGA SEQ ID NO: 864 14 106330425 1.06E+08 IGHJ5*02-X97051 TACTTTGACTACTGGGGCCAGGGAACCCTGGTCAC CGTCTCCTCAGGTGAGTCCTCACAACCTCTCTCCT GCTTTAACTCTGAAGGGTTTTGCTGCATTTCTGGG GGGAAATAAGGGTGC SEQ ID NO: 865 14 106330425 1.06E+08 IGHJ4-U42588 TTTGACTGCTGGGGCCAGGGAACCCTGGTCACCGT CTCCTCAGGTGAGCCCTCACAACCTCTCTCCTGGG TTAACTCTGAAGGGTTTTGCTGCATTTTTGGGGGG AAATAAGGGTGCTGG SEQ ID NO: 866 14 106330797 1.06E+08 IGHJ3*01-M25625 TGATGCTTTTGATGTCTGGGGCCAAGGGACAATGG TCACCGTCTCTTCAGGTAAGATGGGCTTTCCTTCT GCCTCCTTTCTCTGGCCCCAGCGTCCTCTGTCCTG GAGCTGGGAGATAAT SEQ ID NO: 867 14 106330797 1.06E+08 IGHJ3*02-X97051 TGATGCTTTTGATATCTGGGGCCAAGGGACAATGG TCACCGTCTCTTCAGGTAAGATGGCTTTCCTTCTG CCTCCTTTCTCTGGGCCCAGCGTCCTCTGTCCTGG AGCTGGGAGATAATG SEQ ID NO: 868 14 106330797 1.06E+08 IGHJ3*02-X97051 GATGCTTTTGATATCTGGGGCCAAGGGACAATGGT (2) CACCGTCTCTTCAGGTAAGATGGCTTTCCTTCTGC CTCCTTTCTCTGGGCCCAGCGTCCTCTGTCCTGGA GCTGGGAGATAATGT SEQ ID NO: 869 14 106331001 1.06E+08 IGHJ2P*01-X97051 GCTACAAGTGCTTGGAGCACTGGGGCCAGGGCAGC CCGGCCACCGTCTCCCTGGGAACGTCACCCCTCCC TGCCTGGGTCTCAGCCCGGGGGTCTGTGTGGCTGG GGACAGGGACGCCGG SEQ ID NO: 870 14 106331409 1.06E+08 IGHJ2*01-X97051 CTACTGGTACTTCGATCTCTGGGGCCGTGGCACCC TGGTCACTGTCTCCTCAGGTGAGTCCCACTGCAGC CCCCTCCCAGTCTTCTCTGTCCAGGCACCAGGCCA GGTATCTGGGGTCTG SEQ ID NO: 871 14 106331617 1.06E+08 IGHJ1*01-X97051 GCTGAATACTTCCAGCACTGGGGCCAGGGCACCCT GGTCACCGTCTCCTCAGGTGAGTCTGCTGTCTGGG GATAGCGGGGAGCCAGGTGTACTGGGCCAGGCAAG GGCTTTGGCTTCAGA SEQ ID NO: 872 14 106331834 1.06E+08 IGHJ1P*01-X97051 AAAGGTGCTGGGGGCCCCTGGACCCGACCCGCCCT GGAGACCGCAGCCACATCAAGCCCCCAGCCCCACA GGCCCCCTACCAGCCGCAGGGTTTTGGCTGAGCTG AGAACCACTGTGCTA

TABLE D SEQ ID NO Name Sequence SEQ ID NO: 1 IGKV1/OR2-3*01 cccagtgcgacaagtcataacatcaaccgctaggatagcagatgagtgaggccgggttgc cctagatgctcctcctggtgcctcaatctgctgagttgttttccagatgcagccaagttt SEQ ID NO: 2 IGKV1-22*01 cctagagtgttacaggtcataaaataaacccccagggaagcagaagtatgactcatggct gccccaggtgcttccactggtgcctccatctgctgagagtgtttctcaggtgcagccaag SEQ ID NO: 3 IGKV1-27*01 cactgtgatacaagcccgaacataaaccatggagggaagtagatgtgtgaggctgggctg ccccagctgctcctcctggtgccgccctctgctgacagcagttctcagatgcagccaagg SEQ ID NO: 4 IGKV1D-37*01 cacagtgttacaaggcataacataaaccccccaaggaagcagatgtatggggctggcctg ccccagatactcctcctactgcctccagctgctcagagcgtttctcatattccagtcaag SEQ ID NO: 5 IGKV1-39*01 cacagtgttacaagtcataacataaacctccaaggaagcagatgtgtgaggacgagccac cccagatgctcctcctggtgcctccatctgctgagagcatttctcaaactcagtcaggtt SEQ ID NO: 6 IGKV1-35*01 cacagtgttacaaaccataacaaaccccccccaggaaagcagacatgtgacgctgggctg ccccacctgctcttctttgtgcagccatctggtgacaacacttctcagactcagcctgag SEQ ID NO: 7 IGKV1-32*01 cacagtgttacaaacccaataagctccccaaggaagcagatatgtgagggtgggctgccc cagctgcttctcctgtttcctccatctgctgagagtgtttctcagactcagccacactct SEQ ID NO: 8 IGHV7-81*01 caccatgtggaaacccacatcctgagagtgtcagaaatcctgatgtgggaggcagctgtg ctgagctgaggcagtgatgcagcagtttccttaacttccatcttatctcattttgcatcg SEQ ID NO: 9 IGHV1-14*01 cacagtgtgaaaacccacatcctgagagagtcagaaatcctgagggaggtggcagcagtg ctaggcttgagagatgacagggattttatttgctttaaaggctttttttagaaagcgagg SEQ ID NO: 10 IGHC1-69*01 gacacagtgtgaaaacccacatcctgagagtgtcagaaaccctgagggagaaggcagctg tgccgggctgaggagatgacagggtttattaggtttaaggctgtttacaaaatgggttat SEQ ID NO: 11 IGHV1-67*01 cacagtgtgaaaactcatatcctgagagtgtcagtaaccctgagggaggaagcagctgtc ccagttttcaggatatgacaggatttatggggtttaatgttgtttagaaaataggttata SEQ ID NO: 12 IGHV1/OR21-1*01 cacaatgtgaaaacccacatcttgagagtttcagaaactgcagggaggaggcagctgtgt tcctgcagaggagatgacagggaagatgaggtttaaagttgtttagaaaatgggtcaagt SEQ ID NO: 13 IGHV1/OR15-3*03 gacacagagtgaaaacccacatcctgagagtgtcagaaaccccaaggaggagcagctgta ctggagctgaggaaatggacaaagattattcagattgaagactttctacgaaaatgacct SEQ ID NO: 14 IGHV1-3*02 cacagtgtgaaaacccacatcctgagagtgtcagaaaccccaggggggaagcagctgtgc tggcatggaggaaatgacaaagattattagattgaagactttctcagaaaatgatattaa SEQ ID NO: 15 IGHV1-17*01 gacacagtgcgaaaacccacatcctgagagtgtcagaaaccccaggaaggaggcacctgt gctgacacagagggagatgacaaagattattagattaacgattttcttaga SEQ ID NO: 16 IGHV1-17*02 cacagtgcgaaaacccacatcctgagagtgtcagaaaccccaggaaggaggcacctgtgc tgacacagaggagatgacaaagattattagattaaagattttcttagaaaatgacactaa SEQ ID NO: 17 IGHV1-38-4*01 cacagtgtgaaaacccacatcctgagagtgtcagaaagcctgaggaaggaggcagctgtg ctggggctgaggagatgacagggattacttgattgaagactttcttagaaaacgaggtta SEQ ID NO: 18 IGHV5-51*01 cacagtgagagaaaccagccccgagcccgtctaaaaccctccacaccgcaggtgcagaat gagctgctagagactcactccccaggggcctctctattcatctggggaggaaacactggc SEQ ID NO: 19 IGHV5-78*01 gaccatctaaaaccttccgcggtgcaggtgcagagtgagctgccagacacaccctcccca ggggcctctctattcatccggggaggaaacactggctgtttgtgtcctcaggagcaaaaa SEQ ID NO: 20 IGHV3-50*01 gcgaataatggagaacttgagatatggagtgtgagtggatatgagtgaaaaaacagtgat tctgtgtggcaggttctgactcagatgtctctgtgcttgtaggtgtctagtgtggggtgc SEQ ID NO: 21 IGHV(III)-76-1*01 cacaggagatatccgtgtggcaacctaacacaggggacacctgtatttgtgtctgagccc agacacaaacctccctgcagggagacaggaggggaccgtgtgacagacactgctcagaac SEQ ID NO: 22 IGHV3-30-22*01 ccaagtgagagctgaggacatggctgtgcatggctgtacataaggtcccaagtgagcaaa catcggtgtgagtccagacacaacacttcctgcaaaaacaagaaaggagtctgggccgaa SEQ ID NO: 23 IGHV(III)-22-2 acaagagtcagaaaagtgtgcaggaggccgggtgaggctgtagacactgtcagcccacta tgccaatcccaccacgagtgctggagaaggtgggagtctgatgaagcttactaacaaacc SEQ ID NO: 24 IGHV(II)-44-1D*01 gccgagattgcgccactgcactcagcctgggcgacagagcgagacttcgtctcaaaaaaa caaaaaaaaaaatcaatcattggaatactgttgttcattacaattaatgaacgcttgata SEQ ID NO: 25 IGLV(IV)-64*01 cacaggtggggaagtgggacaaaatctcagcctgctcagagtcttgttctctgatgaaat ttagatcttaaaataacttatatcacttgtgtgggatgagtgagatatcccgagctcaca SEQ ID NO: 26 IGHV(II)-23-2*01 cacagcgaggggaagccattgtgcgctcagaacactctacaaattttcctccctagtgtt ttaccaaaactggtatatatttcagatactgaaatatttacaa SEQ ID NO: 27 IGLV(VI)-22-1*01 agtaagaccaaaaccctcctgagattcctggcttgtgtcctgacactggggctgttggga ttcctgtctttccttcaagattgttcaaataagcaccgacaatcacttccatgtgagata SEQ ID NO: 28 IGLV(V)-58*01 aaggcaaagtgaccccagtgaatgaggaagcaggacaaaaactgttttctctgctccact atgaaggctgccacgtggccctgagaaacagtgcctgttttccttactactcaagaaaga SEQ ID NO: 29 IGLV(V)-66*01 ccgtttgggtaaagcacagataaatggggaaatgaggcaaaaactgtttttctactctgc taccaaggttgaaaaatggctctcagaaccagtgtctgctgacctgcatactcaaatatg SEQ ID NO: 30 IGHV(II)-20-3*01 taaaataaaataaaatgtaaaaaatgatcaataaatgaaattactatcagttgaaactca ttaaatttaaagacattttctactcaagtaactataagaacatgaatgtcaagtttcaga SEQ ID NO: 31 IGLV(IV)-59*01 cacaggcagatgagaaagtgagacgaaactcagcctactaagaatggaactatggctctt tttccaattgtcaaataattttcacatacacaaactattttggaagtagctactgattca SEQ ID NO: 32 IGLV7-46*02 cacagtgacagatccatgagaggaaccaagacataaacctccctcggcccttgtgatgtg gagatcacatgatcagacatgccagatcccaagatagcctacatgtggaccagccataga SEQ ID NO: 33 IGLV8-61*01 cacagtgatttaaacctatgaggaagtgcaactaaaacctctttatatactgagaacagt tcagcccttacagacaggagggaaagtgagagggtggaaatggtcaacacggtgagtgag SEQ ID NO: 34 IGLV8/OR8-1*01 tttaaacccatgaggaggtgcaactaaaacctctttacatactcagaaagattcagccct tagaagcaagagagaagttgagagggtgggaatgtcaacaccatgagctgggaacctcct SEQ ID NO: 35 IGLV(I)-56*01 ttctctgattatctggatgctctgtgactccttctgtgcatctctgggatcatcattcag actcacctgcaccctgagcagtaacatcaatgttgtttgctatgacatttactggaaaca SEQ ID NO: 36 IGKV3-31*01 cacagtgattccacaggaaaccaaacctccacaagacagctggtgttttttcctcaagcc ttctgtttacttatgggaagctactatggtggctgcttagttattgagagaaaacaatgg SEQ ID NO: 37 IGKV3-34*01 cacagtaattcaacatgaaacaaaaactttcacaaaaccattgattttttttttctaaaa ccagcagctttatgggctgcagctatgatggctgcccagttttagcaactgtgcctctat SEQ ID NO: 38 IGKV3D-25*01 catactgattcaacatgcaacaaaaacctccaggagacctaaggtgtttatttgattata ccacctgcttcctttttagtcatctgatgtggtgctgctcagttttagcatctctgcttt SEQ ID NO: 39 IGKV3-11*01 cacagtgattccacatgaaacaaaaaccccaacaagaccatcagtgtttactagattatt ataccagctgcttcctttacagacagctagtggggtggccactcagtgttagcatctcag SEQ ID NO: 40 IGHV2-70*13 cacagagacacagcccagggcgcttcctgtacaagaacccaggtgtttttcagtggtgct ccctccccacttctgcagaacaggatagtgtggctgagatgccatttcctgcccagggcg SEQ ID NO: 41 IGHV2-70D*04 cacagagacacagcccagggcgcctcctgtacaagaacccaggctgcttctcagtggtgc tccctccccacctctgcagaacaggatagtgtggctgagatgccatttcctgccagggcc SEQ ID NO: 42 IGLV(VI)-25-1*01 agtaagaccaaaaccctcctgagattcctgacttgtgtcctgacaccaggtctgttcttc cctcccctagaataaaacatctcttaagcacaaggctgaagaaatgtggcctcctccttt SEQ ID NO: 43 IGHV(II)-22-1*01 cacagcgaggggaagccattgtgcgctcagaacactctacaaattttcctccctagtgtt ttaccaaaactggtatatatttcagatactgaaatatttacaacctacgttattatgcta SEQ ID NO: 44 IGHV(II)-30-31*01 caaacaaaacgacacaaaaaattccaaagttgtgcaccctctaaaagcatatgtacttaa ttctcatttttaatttattaaacagctctaataagttcaatgttcctgccttctcagttg SEQ ID NO: 45 IGKV2D-36*01 aaaacttgaacttccatcaatgataaatattccttttgcctcaagcacatatttgaggaa ttttccattgagtagatctaccgataaggtcacatttttctgtctgttttaatctgaata SEQ ID NO: 46 IGHV1-12*02 tagttatttgagagatttttcatacaacatttattctgtaagcaaatttcagggattgtt gaatgaatcatattaacaaatctgacacagaacttcctctgaatcaatctttgtaaacat SEQ ID NO: 47 IGHV(II)-44-2D*01 tgcctggccgtaagttaccatgtgctttttaaaaaaatcatagcaaaggggtgtcttctg gaaatgacattttgaaatggtgttattagaccacccctggaagggacacagtaaccacac SEQ ID NO: 48 IGHV(II)-74-1 agtgatggtgggggtcctactagcctgtggcaaatggaagcatctcttttttatcagact gaataatattgtagtgttttcttataccacatttacttcatccctttgtgcattaacact SEQ ID NO: 49 IGHV(II)-46-1*01 aaaatccattgctagtggtggtgggagtccatttgtcttgtggaaaatggcagcatttcc ttattttataaggcataataatgctatgttgtgtacacataccacattgtctttatccat SEQ ID NO: 50 IGHV(II)-67-1*01 aaaatgcatggctagtgctgctggaaacccattcctactgtggcaaatggcagcatctct tttaaaaggctaaataatattctattctgtatacataccacattgccattatcctttttg SEQ ID NO: 51 IGHV(II)-23-1*01 atagatggataaactaacctaggcctttgaaaataaacccttatctgagagtgaaaagat aagccatagatttggagagtttgcttgcaaatcaaatatttggaaaaggacttttattac SEQ ID NO: 52 IGHV(II)-40-1*01 taggcactggatggaaagcacaggagtgggtcaggtgcatacgtgatgagtggaggatga attccagcccacttatcatgaattcagacaagcccacatgttcccacatgcactatatct SEQ ID NO: 53 IGHV(IV)-44-1*01 cactgtgactcgaatccagagtgaactcagacacaaacctgccctgcaggggttcttggg accacaaggggaaggatcaggtcaccagggtgtacttaggaaccactgaactgggtcagg SEQ ID NO: 54 IGHV(II)-28-1*02 cgcaatgaagggccttcattgtgagcctagacacaaccctccctgcaggggtgaatagga gcagcagggggcattcggggcagtatgggggcttaggatgattgttaggggtcaggatga SEQ ID NO: 55 IGHV(II)-30-41*01 cattgtgagcctagacacaaccctccctgcaggggtgaataggagcagcagggggcattc ggggcagtatgggggcttaggatgattgttaggggtcaggatgagcaggatcaaggcttc SEQ ID NO: 56 IGHV(II)-65-1*01 cacaacgaggggaagtcattgtgagcccagatacaaacctccctgcaggggagctcagaa agagcaggaggcactcaggacaccagggaacactctggacacatcaaggcaggtgcaatg SEQ ID NO: 57 IGHV(II)-51-2*01 aacagaagagatgtcagtgtgatcccagacacaaacttccctggagaggggcccaggacc accaaagagcactcaggcccatgaaaacagggcccaagctggagaacgggtttcctgtca SEQ ID NO: 58 GHV(II)-15-1*01 cacagaaggggaggtcattgtgaggccagacacaaacctccctgcagggaagctcaggac accagggggtgctcagacaccaagggctctcaggacacatcaaggcaggtgcaagagggg SEQ ID NO: 59 IGHV6-1*01 cacagtgaggggaagtcagtgtgagcccagacacaaacctccctgcagggatgctcagga ccccagaaggcacccagcactaccagcgcagggcccagaccaggagcaggtgtggagtta SEQ ID NO: 60 IGHV(II)-60-1*01 cagagtgaggggaccacggtgcgagctcacacccaaaccttcctggaggggtgcacagga cagcaggagtcccgatgatggaagggggtggtctggattccaggtcactctcaagatcat SEQ ID NO: 61 IGHV(II)-53-1*01 cacagtaaggtaaccacagtgggaactcacacccaaacctccctgtgggggtgcacagga cagccacagttactcaggaccccaggattcctcaggacaccaaggggcactcaaggccat SEQ ID NO: 62 IGHV(II)-20-1*01 cacagtgaggggacatcagtgtgagcccagacacaaacctccctatgcgggttcacagga cagcatggggtgctgaggacagaggtgggcactcaggaaccagcagggaaacccaggggg SEQ ID NO: 63 IGHV3-41*01 agtgagaggaagtccgtgtgagcccagacacaaacctccctgcaggggcacgcggggcca ccagagggtgcccaggatcccctgaagacagggacagcccaaaggcaggtgcagatggat SEQ ID NO: 64 IGHV3-52*01 cacagtgaggggaggtcagtgtgagcccagacacaaacctcctgcaggggcatctggagc cacaagggggcgctcaggatacacagaggacaggggcagccccagggcaggtgcaggtgg SEQ ID NO: 65 IGHV3-73*02 cacagtgaggggaggtcagtgtgagcccggacacaaacctccctgcaggggcgcgcgggg ctaccagggggcgctcgggactcactgagggcgggacaggtcccaggaacaggtgcagcg SEQ ID NO: 66 IGHV3-42*03 cagtgagggggaggttaacgtaggcccatacacaaatctccctgcaggggcgcgcagggc caactgggggcgctcgggacccactgaggatgggacaggtcccaggggcgggtgcagggg SEQ ID NO: 67 IGHV3-6*01 tacggtaaggagaagtcagtgtgagcccagacacaaacctcccttcagggtacctgggac aaccagggaaagcctgggacactgtgcactgtgctgaccccaggggcaagtgcaggtgct SEQ ID NO: 68 IGHV3/OR16-9*01 cacagagtgaggggaagtcagtgagagcccaggcacaaacctccctgaaggggtcccaga aacgactagggggcgccaggacactgtgcacggggctgtctccagggcaggtgcaggtgc SEQ ID NO: 69 IGHV(II)-44-2*01 aacagtgagaggaagtcaatgtgagtccagacataaaccttcctgctgagaacaatggaa agcttttcttctaagataaggaataagaaaagaatgcccagtcttaataattctaatcag SEQ ID NO: 70 IGHV3-25*02 cacagtgaggggaggtcagtgtgagcccagacacaaacctccctgcagggccatgcgggt ggtttcctttctcagctgcaggaggcgggcttattgttgcaggactctggagacttatta SEQ ID NO: 71 IGHV(II)-26-2*01 ctcagtgaggaggtgtccttatgagccctgacacaaacctgtcagggcacttaggacctc caggaagactcaagaccaccaaggggactcacgaccactggggaagggcaggttgcagta SEQ ID NO: 72 IGHV(III)-67-3*01 cacagcgagggacatttctgtgagtccagacagaaacctccctgcagggagacaagagag gactttgtgataaatggtgcttaggacaccagggggcactcaggacagcagagggtgctc SEQ ID NO: 73 IGHV(III)-47-1 cacggtgaggggacatctgtgtgagctcagacacaaacctgcctgcagggagacacaaac ctccctgcatggtagatgcttctcagaaccaccagggggtgcacaggaaaccagaaggtg SEQ ID NO: 74 IGHV(III)-82*01 cataggagcaggaacatctgcgtgagcccagacacaaaatcctctgcagggagacaggag ggaatcgcatggtagatgctgattggaactaccatgtgtcgctcagaactaccaggaggt SEQ ID NO: 75 IGHV(III)-67-4*01 cacaggagagagattatctgcacaagcccagacacaaaaatctgcagggagacaggaggg aactgcatggtagatgctgctcagaagcaccagggggcactcaacacaagggggcgctca SEQ ID NO: 76 IGHV(III)-16-1*01 agacacaggagagggaatatctgcgtgagcccagacagaaaaatctctgcaggaagacag gagggagctgcatggtagatgctcctcagaaccaccagggcaccttggggacaacctggg SEQ ID NO: 77 IGHV3-57*02 cacaggagagggaatatctgtgtgagcccagacacaaaaatctctgcagagagacaggag ggaactgcatggtagatgctcctcataaccacaaaggggcagtcaggaccatcaggagga SEQ ID NO: 78 IGHV(III)-5-1*01 cacatgaggaaaggccggtgtgagacacaaacctccaggaacacctgggctaatgagctg cagggggcgctcaggacccactgatcagtcaaccacagaggggagtgcaaaggttaggac SEQ ID NO: 79 IGHV3-63*01 ccaagtgaggaaacatcggtgtgagtccagacacaaaatttcctgcagaaagaagaaagg attctgggccgaaggggacactcagcactcacaaaacaggtggagccccagggcaggtac SEQ ID NO: 80 IGHV3-54*01 gtcaccaggtaagaagacatcagtgtgatcacagacacagaatttcctgaaataagggag gagtctgggctaaaagggcactcaggacccacagaaaacagcggaagctctagggc SEQ ID NO: 81 IGHV3-54*04 caccaggtaagaagacatcagtgtgaacacagacacagaatttcctgaaataagggagga gtctgggctaaaagggcactcaggacccacagaaaacaggggaagctctagggcaggtgc SEQ ID NO: 82 IGHV3-79*01 agaagacatcagtgtgaacacagacacagaggttcctgtaatgataagggaggaggctgg gataaagggagcactcaagacccacagaaaacaggggaagctctagggcaggtgcagacg SEQ ID NO: 83 IGHV3-30-33*01 caccaggtaagaagacatcagtgtgaacacagacacagagtttcctgcaatgataaggga ggaggctgggctaaaaggggcactcaggacccactgaaaacgggcagctctagggcaggt SEQ ID NO: 84 IGHV3-30-2*01 ccaggtaagaagacatcagtgtgaacacagacacagtttcctgcaatgataagggaggag gctgggctaaaaggggcactcaggacccactgaaaacgggcagctctagggcaggtacag SEQ ID NO: 85 IGHV3-9*01 cacagtgaggggaagtcagcgagagcccagacaaaaacctcctgcaggaagacaggaggg gcctgggctgcagagggcactcaagacacactgaaaacacggttaacactgggacaagtt SEQ ID NO: 86 IGHV(III)-51-1*01 catcgtgatgggaagtccacgtgggctcagagacagactgccatgcaggacacagggggt ggcttggctgaagggggcactcagcacccacagaagacaggagcagcccagggcaggggc SEQ ID NO: 87 IGHV3-62*01 cgcagtgagaagtcagtgtgagcccagacacaaacctcctgcagggtacctgggacaatc agggaaagcctgggacactgtatactgggctgtccccaggggcaagtccaggtgatataa SEQ ID NO: 88 IGHV3-19*01 cactgtgagaggacggaagtgtgagcccagacacaaacctcctgcaggaacgttggggga aatcagctgcagggggcgctcaagacccactcatcagagtcaaccccagagcaggtgcac SEQ ID NO: 89 IGHV3-76*01 cacagtgaggagaagtcagtgtgagcccagtcacaaacctcctacaggaacgctgggagg aaaatcagctacagggctcactcaaggcccactgatcagagtccactccagagggaggtt SEQ ID NO: 90 IGHV3-37*01 catggtgaggggaaatcagtatgagcccagccagaaacctccctgcaggaaccctggggt ggggggaaatcagctgcagggggcactcaggacccactgatcagaatcaaccccagaagg SEQ ID NO: 91 IGHV3-23D*01 cacagtgaggggaagtcattgtgagcccagacacaaacctccctgcaggaacgatggggg tgaaatcagcggcagggggcgctcaggacccgctgatcagagtcatccgcagaggcaggt SEQ ID NO: 92 IGHV3-53*02 cacagtgaggggaggccattgtgcgcccagacacaaacctccctgcaggaacgctgggga aatcagcggcagggggcgctcaggagccactgatcagagtcagccccggaggcaggtgca SEQ ID NO: 93 IGHV4-39*07 cacagtgaggggaggtgagtgtgagcccagacaaaaacctccctgcagggaggctgaggg cgcggtcgcaggtgcagctcagggccagcagggggcgcgcggagctcacggaatacaagg SEQ ID NO: 94 IGHV4-55*02 tacacagtgaggggaggtgagtgtgagcccagacacaaacctccctacagataggcagag ggggcgggcacaggtgctgctcaggaccaacagggggcgcgcgaggcacagagcccgagg SEQ ID NO: 95 IGLV11-55*01 cacagtgagacagatgaggaagtcggacaaaaaccaaggttttaagcttgtcatttttac tgaactggttaagaacttcagtggttaataaaatcacattaaatacaggattgttgttaa SEQ ID NO: 96 IGLV(IV)-53*01 cactgtgctctaggccaatgggaaaatcccctctgcttgtgctgcctgggctcccactag gcccctgctgtttgtgacaacagccagcactggtggtgacgcttcagccatgtatgccct SEQ ID NO: 97 IGKV6D-41*01 cactgtgctacaacccaaaacaaaaattagctcagcctggcggaacagagaaactgaaca ataccccgtttttatgatccttgcaggtgcagttggggaaataatttaccaaataccatc SEQ ID NO: 98 IGKV7-3*01 cacagtgctttaggtctaaacaaaaacctccccaggcagctgctccctgaggctcaaatc cctcagatgtggctttttatgcaggtccatcagcctgctgtcataggcttgtttgaacaa SEQ ID NO: 99 IGKV2-23*01 cacaatggttcagcaccaaacaaaagcctcctgcttggattgtcccagctgcccaaatta gttccttcactgaggagtagacagggtatatgctctaaatctatgtaacaggaagatgtt SEQ ID NO: 100 IGKV2-18*01 cacagtggtacaaccctgaacagaaacctcccttcttgctgtggttcagctgcccaaatg tgttgtttatctggaaagcagacactgtctattatcttgggagagtaaagagaggaagat SEQ ID NO: 101 IGKV2-4*01 cacagtggtaaaaccctgaacacaaacctccctacttgggatggcccagccatccacaag tgtttgcacgtggactgtctgcatggcagattctgagttggcttcacaggtagatgttag SEQ ID NO: 102 IGKV2/OR22-4*01 cacagtgctacatcctcgaacagaaacctccctgctggttgacccagctcgcgcatgggc tgcttgtctgagggaacagctgagcagagtctttgagtctgcagaggagaaggctgttgg SEQ ID NO: 103 IGKV4-1*01 cacagtgcttcagcctcgaacacaaacctcctccccatacgctgggccagtaggtctttg ctgcagcagctgcttcctctgcacacagcccccaacatgcatgcttcctctgtgtgttgg SEQ ID NO: 104 IGHV4-80*01 gggaggcggagggggcgggcgcaggtgccgctcaggaccagcagggggcgcgcggggccc acagagcaggaggccgggtcaggagcaggtgcagggagggcggggcttcctcatctgctc SEQ ID NO: 105 IGLV2-11*01 ctcagcctcctcactcagggcacaggtgacacctccagggaaagggtcacaggggtctct gggctgatccttggtctcctgctcctcaggctcacctgggcccagcactgactcactaga SEQ ID NO: 106 IGLV(I)-70*01 tgcccttggcctgtcccgaggctgatcactccatacttgcctatgacaaacaaagagggt gcctgtggctgatcgtacagtttaagcaagggaggaagtgagactcagccacaggcccct SEQ ID NO: 107 IGLV(IV)-66-1*01 cactgtgctccagacttacggggaagtgagattagaacctcccctgcattctctctgcct tgtgcaggcaacaatacactgtctgggaccgagtgtggctcatcagtagcagctttgttg SEQ ID NO: 108 IGLV5-52*01 cacagtgctccagacccatgaggaagtaagacaaaaccctcccctctactctcctggtct agtgaaatcacccctgctggtggctctgaccaaatctagctcagggggtgacatctgttg SEQ ID NO: 109 IGLV1-62*01 tacagtgctccaggcttgcaggggagtgagacaagaacccccttcctcctttcccaggag ggtgagtgcccagcagctactgcacaggcctggcctgtggcttctgcagttgctgtttcc SEQ ID NO: 110 IGLV6-57*01 cacagtgctccagacccatggggaagtgagacagaaactccccagagcatctctacctgg gccagtctcagcctgtctccaccagagagggtagctctcccatctctcctgtctaagtgc SEQ ID NO: 111 IGLV(I)-20*01 caccgtggtccaagttcatggggaattgagacccaaacctgccctgggctctcagcctct ctcttgttctgaagatgcttcctcaccctgtgcaaggggcttcttgcagcactgccttga SEQ ID NO: 112 IGLV8/OR8-1*02 tccacagtgatttaaacccatgaggaggtgcaactaaaacctctttacatactcagaaag attcagcccttagaagcaagagagaagttgagagggtgggaatgtcaacaccatgagctg SEQ ID NO: 113 IGLV3-17*01 cacagtgacacagacagattggaaagtgagatctaaagaccttcactgtctgtatcaccc tctttctccagccatagcaggactgagcagggctggcccgggtcacctggatcgaagccc SEQ ID NO: 114 IGLV3-26*01 cactcatgggacagcagtgctactcacctcacaatgacacagacagattgggaagtgaga tctaaagaccttcactgtctgtgtcaccctcttcctccagccatagcaggactgtggaga SEQ ID NO: 115 IGLV3-29*01 cacagtgacagaggcagacaaggaagtaagacacagaccccttccccatctgtgctgctg tcgtcctccagcccggcaacactgtggacaaagccatgagcatgcatgacccagttcacc SEQ ID NO: 116 IGLV4-60*02 cacagtgatacaggcagatgaggaagtgggacaaaatcctcaacctgctgaggctattgt tcagtgacaatttttaattttaaaacattttctgtatgtaaaaaatctatctggatgcat SEQ ID NO: 117 IGLV10-54*02 cacagtgcctcaggccagtggggaagtgagataaaaactcaagagctccctcggcctcac tgaacaggcctcacagagcactgtttaaactggaccacccaaaagacaagggatgcattc SEQ ID NO: 118 IGLV10-67*01 cacagcgcctcaggggaagtgagacgaaaactcaggagctcccctagcttcactcggtat gcgggggcgtcatagagcactgtttaaactaaaccaaaaatgacaagggctggtttccac SEQ ID NO: 119 IGLV(I)-42*01 aacagtgctgcagtctgggaaagtgagatgagaacacgccaggtctcctaggagcatgac cttccaatggcaccacccacaaccaggacacgctggtcttgttttaccatttgtgtggat SEQ ID NO: 120 IGLV2-28*01 cacagtggacataagattgattctcaggctccaagtctggccagtgagcttctttgagac tccctgggatcccagcagtgacactgatcactattgctgtcccacacatcccaagtgatg SEQ ID NO: 121 IGLV(IV)-65*01 cagcactccagacccactgggaggttacaaaaacctcttctctgatctcctggcctggtg tagtcactcctgctggtggctctaataaagtctatctcactgggtgacttatattttaga SEQ ID NO: 122 IGLV(I)-63*01 cacagtgctccgggttgaagtaagtcagaccaaaacacacagtgtgcccagccatgaagc tctcccatgcaccccctactctgcagctaagtcaatgtgttctctcacttgtttgtccta SEQ ID NO: 123 IGLV(I)-68*01 ggcagtacttcaggccagtggggaagtgggagaaaaagctgctgcccatccagcaatgga gcttctctgtgcagcccccacttcttgggcaagtcagctgattaacgttgcttttcattt SEQ ID NO: 124 IGHV(II)-28-2*01 acacctggcctcttcgtttttattcatatattccttcagcagccactatgtcttcccact gatttcttcagtttctgccttttccttttgaataaggctgttactcctgagggaagatgg SEQ ID NO: 125 IGHV(II)-44-3*01 ggcaggccaccaagtccagctaatttttgtatttttagtagacactgggtttcacaatat tggtctggctggtctcaaactcctgatctcagcctcccaaagtgctgggattaaagccgt SEQ ID NO: 126 IGHV3-36*01 attgtgtgcatcccttgtttaggtacatgcagagatgctgctttggtgtgttcaggggct cctgttttggggacaccaattttggagtttgcagtatccttgagtccagtacgttcatgg SEQ ID NO: 127 IGHV(III)-25-1*01 atggtctcactgatatctttacttcttttatcacttttgttatgtaaatcacaatgaata gtgtattcctcatctattatacatttgttaagtcttttttggtgtctttaaaaaaactga SEQ ID NO: 128 IGHV(III)-25-1*02 cacaatgaatagtgtattcctcatctattatacatttgttaagtcttttttggtgtcttt aaaaaaactgataactttatagtatgtaatatccttaagtcctgaaagtgttttttgatg SEQ ID NO: 129 IGHV(III)-11-1*01 cttcatctattatacacttgttaagtcttttttggcatcttttaaaaaactggtaacttt atcctgtgtaatatccctgttaagtcctaaaagtcttttttgatgtctattttttcttaa SEQ ID NO: 130 IGHV(III)-20-2*01 tacctaaatgtgtgtgggggaagcagggggtgttattctgttgttctgtgttctctgaga tgcatggattcaccatttactctgcctccattttggggaacacagttagaaaaaatgtca SEQ ID NO: 131 IGHV(III)-44D*01 tggttttcagcagttttaataagattcacctaaatgtgtgtgtgtgtgtcgaggggtgtt atgctattgttctgtgttctctgagatgcatggattcaccgtttactctgtctccatttt SEQ ID NO: 132 TRGV1*01 cacagtgattcagacactgaaaatctgcctgtggttgcttctggtacacaagatagacca gccaactctcatttcctgccctgaatttactgtattctgtacaaagagaaacacagctta SEQ ID NO: 133 TRGV4*01 cacagtgattcagatccgccctacaccacactgaaaacctgccttgtggctgcttctggt acacaagatagagctgccccctctcatttcctgccaccaaatttaccgtgtgctgaacaa SEQ ID NO: 134 TRGV9*01 cacagcagcagacagtttgagccatcccattcaataaatgtttattgagtctttgtttat aattacgaattgggaagccacagttaccaccagtgtgcttgtaaacagtttttaagataa SEQ ID NO: 135 TRGVA*01 cgcagccttgcatgctgccccagccctacacaaaaggactcttcctcccgatccaacaag gccttgggcattttcacttactcttggtcccttgggtttccctgtggcatagaagaaaaa SEQ ID NO: 136 TRBV8-1*01 caataatggcaatgtggcagtttccatacatatgtttgtgctagcttttttattattata tagtaaacttctttgcctctttttatagttattgtcttgaaatatattttatctgatata SEQ ID NO: 137 TRBV22-1*01 cacaatggaagcacaaccattgtctctctgtgcggaaatgtgtcctcaccctacagcccc caccacatcctctagcttaattttttcatttttaatattttcttgagattttactatgtc SEQ ID NO: 138 TRAV1-1*01 cacagtgactatgaggcctccttaactgtgccaaaattcaaaagacaatcagtggagtac aggtgggcttgagaagttctagaacttcctgagtgtatctttgcttaccgtctaatttta SEQ ID NO: 139 TRAV1-2*01 cacggtgactatgaggcctctttagctgcaccaaaattcaaaaggcaaccacagcagcga gaagctgtatttcctgagtgtatgcctgctgtgagttaagactggggactttggaaccag SEQ ID NO: 140 TRAV8-5*01 tcaggaccctgtgataattgtgttaactgcacaaattatagagcatgtgtgttcaaacaa tatgaaatctgggcaccttgaaaaaagaacaggataacagcaatgttcagggaataagag SEQ ID NO: 141 TRBV21/OR9-2*01 cacagtgccgaatgttagcccttcttagaacacaaactcattatggacccagctcaggaa ataagtgtatgtcaggttggtacacactataataacagaaagccaacttgaaagacaata SEQ ID NO: 142 TRBV16*01 cacaatgttaaatattagctaatcttaggacacagactcatcacggactcagctcaggaa gcaggtggtatactaggttggaaggaaataacagaaactagagctagcttaagccaaagg SEQ ID NO: 143 TRBV23-1*01 cacagcactgaaatgtcagttcctcttagcacacaaacttgtcacagacccagctcagga agcaggtgatgtattaggctggaagggagtaacagaaaataactggagccagcttaagcc SEQ ID NO: 144 TRAV40*01 cactgtgttaaaagcacagtgggagctatacaaaaacctcaaaggctcagaggaagtatg tagtgaggctggaaaacccaggttgtagagccctgttctctctttcacagacagtcctgt SEQ ID NO: 145 TRDV3*01 cactatgatgcaggtgcccaggaagtcataacacaaactcctggggcacagctcagcaga gctgcctcttagggcaggtcatgtctgggacttggcatccttctcttagccattttgggt SEQ ID NO: 146 TRAV2*01 cacagaggcagggaacccatgaagagctgaacagaaacagagatcacagcctttgcagga ggcaaaacagagatgagcaataactttttcctccttaattcagtattacccaagcttttt SEQ ID NO: 147 TRAV16*01 cacagtagctggttttgcaaggaagcagaacacaaaccctttaaatacaggaaatatttc tttgcaaactctctgtatggccacagcagggcattctttctccagaaattaatattgagt SEQ ID NO: 148 TRAV8-7*01 gactgtgcctgggactgcaggaggagctgaacacaaacttcctgagacactgaggttttc aggaactcaagggcacagcctgacctatttgtagcaaggtctctcatttgatgaaagtga SEQ ID NO: 149 TRAV8-6*01 cacagtgcctgagactgcaggagagctgaacacaaacctcctgagatgctgagactttct gtgactcaagaactcaacctgtggagctttcaagagggtcccttttttctgtgcccgttt SEQ ID NO: 150 TRAV3*01 cacactgataggggctgcagggggagcagaacacaaactcttgagtctggtaaagcccat tttcttgaagtctttgttccttcacatgagaacggtgtgcttccaggatatgtcacttat SEQ ID NO: 151 TRAV8-1*01 cacagtgtctgggactgcaaagggagctgaacacaaacttcctaaggtgctagggagaat aactgcctctgaaagattttggattctgtcacagtagaaaccatgatgttagtattttta SEQ ID NO: 152 TRAV18*01 cagagtgggagggactgcagcgagagcccagcacaaaccctggggaacgcaggtggggcc tgggtgtgagccgctttgggagatgaatgaatatggactcttgttcgctgggaccccaaa SEQ ID NO: 153 TRAV9-1*01 cacagtgacagggactgcaggggaagctgagcacaaactctgagcagcacgaggggcctg gctgctgagtgtaagccactgtgatcccctctggttagggaccaggaactactctactat SEQ ID NO: 154 TRAV31*01 cactgtgaagaacatgttagaagagccttacaaaaagatcggaactcaacctgaggcaat tgcctattcccacattctcaggaaaaactcacaaaccttacccaggcatttgttagcagc SEQ ID NO: 155 TRAV38-1*01 cacaatgagatgagcagcagggagaggcttacagaaacctcagacctcagcatctgtgca aaggtcacagggtgagagggaagtggtagggtaataggtatagaaaatcattgacttctc SEQ ID NO: 156 TRAV19*01 cacagtgagatgggtgcctgtgggagccctacaaaaacctcaacaagaggcagggctcct ggggagagactctgtcacagacaggaagaagcaaggagggtctgtgtcagcacaggtggt SEQ ID NO: 157 TRAV14/DV4*01 cacagtgacagaactgtcggagggaggtgtacaaaagccctggggacctgcttgagacct ccacctgctggagaaccaaggcgggaaatcaacatcacagacaggaagtggcta SEQ ID NO: 158 TRAV33*01 cacagaagtagaaatgacagtggaagataaacaaaaaccttagcactccataaaggaagc cacctgctcaggagcttagggaaaatacatgaagcacagacaggaagaaggcacattagt SEQ ID NO: 159 TRDV1*01 cacagtgtttgaagtgatagtaaaagcaaaacaaaaaccctagggctcaataagagaacc cctctactccccatcctttgctacaggagccaatctgaaatgcacacctgcagatctcag SEQ ID NO: 160 TRDV2*03 caccctgctgcagctctacttctgagcagctcaaaaaccactgaccaggcgcggtggctc acacctgtaatcccagcactttgggaggccgaggtgggtggatcacgaggtcaggagatc SEQ ID NO: 161 TRBV30*01 cacactgagctgggtggggcagacatctgtgcaaaaaccccaccctctcctgagccctaa ccatactccccaggggccttcacttagggactgggtggaggatatttgtaagtaggtttc SEQ ID NO: 162 TRBV20-1*01 cacagcgccaggaggggatcagacaccgcggcaagaacccctgcagctgccctccgcccc agcgggccccctgagtgctgagaggggaagcgtggagaatggaaaaccacagctttcctg SEQ ID NO: 163 TRBV29/OR9-2*01 cacagtgcagggcacagatcaaagatctaagcaagaacctcagctcccttctacccagct cccctcacatgaacctgagggccctgtcaaggtgggacagaagaggaaaccacagctctt SEQ ID NO: 164 TRBVB*01 gccacacacactcaagatgccccagacaccctgcactccgatcttactcgttcctttact gttttcatcctaattgccctcttacacatttgaccacacatttttggtcttggtggttgt SEQ ID NO: 165 TRGV10*02 accatactagaactgttgaaacaacatgcacaaaatcccctcccagggtctgtgcccacc acatccttcccaacaggggcaaccacagccagtccccagctgggctcccagactcaggct SEQ ID NO: 166 TRGVB*01 cacagcatcagtgccacactgtcccacacaacaacctctgttgggtctctgcccaaccac atccttcccatgggagcaaactctatggactcctagctgggctcccaccctcagccttgc SEQ ID NO: 167 TRGV11*02 cacagtgttagagttgtcaagataacctacacagaaactatctccgagtctgtgcctgtc cacatccttctccatgtgggcaaccacagcggtttgctcagctgggtgcccagccggagc SEQ ID NO: 168 TRAV4*01 ctcgtgggtgacacacagtgagacagatgggcctgcacctgtgccgttttcctctgtggg gtgggagtcacagcctagaaagaagtccaaaagtgctttctaaaatttttattttcaaaa SEQ ID NO: 169 TRAV26-1*01 cacactgggacagatggggctgcacctgtgcaatatctccctggtggcaagtgaggagga gggtagcattcacctagagcaaaatgtcgataggagtcaaaaagtaacaagaaaagagga SEQ ID NO: 170 TRAV26-2*01 cacagtgggacagatggggctgcagctgtgcaatatctccctggtgatgaaagggaaggc atctaacgaggccactgcacaagaaggagcagaagtttaatagaggaagaagaaaattta SEQ ID NO: 171 TRBV10-1*01 cacagtgctgcacagctgcctcctctctgcacataaagggcagttagaatgactgaggtt gcctgtgctcccaagtcccagccttcacaggagtcggagagccctggctagcctgggggc SEQ ID NO: 172 TRBV10-2*01 cacagtgctgcacagctgcctcctctctgcacggaaacggcagttagaaaaactgaggtt gcctgtgcacccaagtctgggccccaccctgggacgtctcagcccccataggagtcacag SEQ ID NO: 173 TRBV10-3*01 cacagtgctgcatggctgcctcctctctgcacgtaaacagcagttagaaagactgaggtt gctctgtgtctatccccacccttggaagtccaggcctccatagaagtcagagggccctgg SEQ ID NO: 174 TRBV28*01 cacagcgcagcacagctgcatcctctctgcacaaaaagagcggacgtaagagagaagggg ccctaactcagggctggtgctggctccgatggcacattcgtgctaaatagaaaaaaagcg SEQ ID NO: 175 TRBV6-2*01 cacagtgctgcacggctgtctcctctctgcacagaaaggcaagggaaggtgctgccctcc tccgcagcacagattcagcgatgcccttggtcctagcaccgaaaactttggagccccaat SEQ ID NO: 176 TRBV6-4*01 cacagtgctgcacagccatctcctctctgtacataaatgcaggggaggctctgccctcct ccccgaccccagactcaaccatgtccttggcagagttctcagcactgggaatcttggaag SEQ ID NO: 177 TRBV6-9*01 cacagcgctgcaagcctgtctcctctctgcacataaaggcacagaggctctgccctcctc ccacccaagactcaaggatgccctgggcagagttctctgcaccaggaaccttggaaccca SEQ ID NO: 178 TRBV6-7*01 cacagcgctgcaaggctgtctcctctctgcacataaaggcaagggaaggtgctgccctcc tcccccacccaagactcaaggatgccctgtgcagagatctctgcaccaggaaccttggaa SEQ ID NO: 179 TRBV6-5*01 cacagcgctacaaggccgtctcctctctgcacataaaggcagggaggttctgccctcctc ccccacccaagactcagggatgccctgggcagagatctctgcgccaggaaccttggaacc SEQ ID NO: 180 TRBV19*02 gccagtagtatagacacagtgaagcacggatgtcgcctctctgtgcataaatgtgcccag tcctgcttccccgaccaggtggcagggctcctctgcactctatgatggcagg SEQ ID NO: 181 TRBV19*01 cacagtgaagcacggatgtcgcctctctgtgcataaatgtgcccagtcctgcttccccga ccaggtgacagggctcctctgcactctatgatggcaggaaacgccactcagccactaagc SEQ ID NO: 182 TRBVA*01 cacagcactgcacaggcatgtgctcacctcacaaaatggcagtctcaaagggaggagtgc ccacccacaagaggctccaccctattctgagaaagaacttctttcagaggaggagagaat SEQ ID NO: 183 TRBV26/OR9-2*01 cacagcactgcatagctgccacatcctctccacataaaaaaaggtgcataccaaagagga aaagcctgccctcaaaattcctcaccgcaaataagagaagttacctcacaggtattgaca SEQ ID NO: 184 TRBV25/OR9-2*01 cacagtgctacatagataccgacactctgcacagaaagggtcgcctctaaggtgaggaca tcttgccttcagaaaccttatcttaaactacagaaacccctgcaaatcttcccagactcc SEQ ID NO: 185 TRBV27*01 cacagtgttgcacagccagctgctctctgcacaaaaacagagggtagctgcaagaacaag gagactcctccttcaggagacccctcaccgaccaacaggataaacttcctccatcatccc SEQ ID NO: 186 TRBV8-2*01 cgcagccctgcacagccagctgccctctgcacaaaaagggcagtcacaggctggaggtgg gcactccttatggaagcccgtgtctcaaccagaagaaaaagctgccctttctgaagctct SEQ ID NO: 187 TRBV24-1*01 cacagtgcttcttggccacctgctctctacacagaaagacagacacatgggtgagttgtt tgctctgaagggtacctggatgtgggttgtgggatgtggggtgtttagagctttcagtgg SEQ ID NO: 188 TRBV2*01 cacagccttgcaaagacaactccagcctgtgcaaaatccctcacagagctgcctccctcc cagccgccagctcccacttcctgcctaagaaaaggaagtctctggttgggtttgttcttg SEQ ID NO: 189 TRBV11-1*01 cacagcgttgcagagactttctctcctgtgcacaaaactccagggctctctccgctctac tcagctcacagcagcctttccttattcctcatcctctcagggaagaagtgagttttcaga SEQ ID NO: 190 TRBV11-2*01 cacagtgtagcagagacacttccctcctgtgcagaaaaccagaaaaccgcaggactctct cctctctactcagctcacagcagcctttccttattcctcatcctcccaaggaagaagtga SEQ ID NO: 191 TRBV11-3*01 cacagtgtagcagagacacttccctcctgtgcagaaaaccgcaggactctctcctctcta ctcagctcacagcagcctttccttattcctcatcctcccaggaaagaagtgagttttcag SEQ ID NO: 192 TRBV15*01 cacagagctgcagtgcttcctgctctctgttcataaacctcattgtttcccagatccagg tgctttctctaggacttctccctcaccacctcttacaacaataggaagtgggttggtggc SEQ ID NO: 193 TRBV12-5*01 cacagcgctgcagaatcacctgctccctgtgcagaaaccctggtgcttcctcttctcctc cagtacccagcagctctcagcagcctttcttgctcctcccctagcacaggaagtacatag SEQ ID NO: 194 TRBV12-1*02 cacagcactgcagaatctccccatctctgtgcagaaaccctggtgcttcctcttctcccc acagctctcagcagtcgtcagcaaagtctttcctgctctctgctcaccatggctcacgcc SEQ ID NO: 195 TRBV7-3*01 cacagcatgacacaatcgcctccttcctgctcataaacctcctcctctctctccttgctt ccttatgatactattttgcaccaggggatcctcatctcacaccactccactgcctcttcc SEQ ID NO: 196 TRBV7-9*01 cacagcatggcacagtcgcctccttcctgctcacaaaccctcaggcacttacttctcctt ccagctctcagaagccctgaacaaaggagctgccctgctctttcctcagcaaggagaatg SEQ ID NO: 197 TRBV7-2*01 cacagcatggcacagtcgcctccttcctgctcataaacctcatccttctctctccttgca gctcctagacacccttaacagaggcttctctttgcttctccctccccatgggaaacaagt SEQ ID NO: 198 TRBV7-5*01 cacagtgtggcatagtcgcctccttcctgttcacaaacctcatccttctctctccttgca cctcctagagacccttaacagaggcctctctttgctcctcacttttgatgggaaagaagt SEQ ID NO: 199 TRBV17*01 cacagcatggctgagtcagttccctccagggtgcaaaccctctggctgctcttctcccag ttgaactccaagaaaacatttgaaaaagcctcttccttatcttcctaccccagaagaaag SEQ ID NO: 200 TRBV5-7*01 cacagcccagcagagtcactgacattctgtatataaacttccgccttagctttgacttga gaactgcaggccccacccaggtttcactccttcaagggaagcttttagttgtttggaagg SEQ ID NO: 201 TRBV5-6*01 cacagcccatcagagtcactgacgttctgtatataaacttcctgccttagctttgccttg agagctgcaggccccacccagatttcactccttcaagggaagcttttagttgtttggaag SEQ ID NO: 202 TRBV5-1*01 cacagccctacaaagccaaccacattctgtgcacaaacctccctggcccaatgtggagca acctcagccctgacatatctgtgagaacctggggactgcagggagaaagaaaggcaattt SEQ ID NO: 203 TRBV5-3*01 cacagccctgcagagtcactggaactctgtgcactaatctctctgcttccgtgtacagca gtctcagaccagacagctgtgagaacctggggccttcagggggaaagataaacaatttca SEQ ID NO: 204 TRBV5-2*01 atgcaggcctgcagagccaagaacattctgtgtacaaacatccctgccccagtgtggaga acttcagccctaacatatctgtgagaacttgaggactgtagtgggaaagaaaagcagttt SEQ ID NO: 205 TRBV4-1*01 cacagccttgcagagtcaccgctttcctgtgcagaaaccttcggggcctgccaggaagcc gtgggggccacggagggctcgggtgaacatttcctccaagagccccgaagaagcttcaga SEQ ID NO: 206 TRBV1*01 cacagccctgcagagtcaccgcctccctgtgcacaaacctcctggatctaatcagaaaac cgtgggggcaacgcatccagctgagcctcagcactcggttcagcattctgtaagacctca SEQ ID NO: 207 TRBV3-2*02 acacagccttacagagccactgcatccctgtgcacaaacctcccggctcagccaggaagc tgtgggccgtgtgtgcacctgcacccaaggctccagtctccattccctgatggcctctga SEQ ID NO: 208 TRBV18*01 cacattgatgcagagccacatcctctcagtccacaaacatcctccagacctgccttggaa acagcggtgggccaggaagggaaacgcgttacctgtacagtgaacaggtcagctctacgg SEQ ID NO: 209 TRBV9*01 cacagccctgcatgagcatcagccttctgtgcaataacattcctgccccactcaggaagt gacggtgaggggagggctgccagccagaggggctcaggccctggagagtggacaggcctt SEQ ID NO: 210 TRBV13*01 cacagaccctggagaattactggctttctgtacccaaaccctcctatctcacttgaggat gtaatagggagaaggaggtgggggctgccacacaactttagccaagccccagagatgctt SEQ ID NO: 211 TRAV34*01 cacagcgattttcaggcctctatcagctgtctccaaacctgcagctgggccacatatgct cttctgacatggggctcctgagatgtggctgggacctttgccaagacatgaagtctcaga SEQ ID NO: 212 TRAV30*01 cacagtgatacccaggcctccaagacctgtactcaaacctaaagctgagccgcagatgct cccctagcacagatgcccaccacaggagtatggggaacttaccagaaggttcatccatga SEQ ID NO: 213 TRAV7*01 cacagtactccctaggcacctgcaacctgtatccaaacatgcagctgggtagaagtacca taacagaagcatcagcaataggggccctgagcctgagtagacgtgaagaactaaggcatg SEQ ID NO: 214 TRAV22*01 cacagtgctccccaggcacctgcggcctgtacacaaaccctcatccgggctcggttcctc taccagtaacaaccacatcacgaggccaccgcagcagcattttgcacagcttaatattcc SEQ ID NO: 215 TRAV6*01 cacagtagtgccctggcagctgcttcctgcacccaaactctgctaactctcacaatcaga gctcatggctgtgctgtctcccaaaggctaatcacagctcctgacagaatgggggggtgt SEQ ID NO: 216 TRAV27*01 cacagtgctcttgaggcacctgctgcctgcacccaaaccctgctgccagccccagtcacg aggctgccacatgcctccagctccgcctcgcacagcttatggcatgaatagagagaacaa SEQ ID NO: 217 TRAV20*01 cacagcgttccccaggcacctgcaacttgtatcaaaaccctgcagctgaggatctgaaat gatggcagaggtatctctgctgttcttcctcttgaaggagtatttatttaatgcccagga SEQ ID NO: 218 TRAV36/DV7*01 cacagtgctccctagtcacctgcagcctgtactcaaattctacagctgaggctctgcaac tgtaagatggggaacttgctacattgagcaagccctcaaaaataaactatacggaaaagc SEQ ID NO: 219 TRAV21*01 cacagtgcacaacaggcacctgcaaccaatacccaaactctatagctggggctctaactg catgttttatcttgagactgagcaatgtttttgcattaagaggacttctaaattgacact SEQ ID NO: 220 TRAV41*01 cacagtgctccccaggcacctggagcccgtacctaaactctaaagttgaggcatcatttc ttactcctgtctttcagacttgtctgtctctatccttggtcagatgatgtaaaatgttta SEQ ID NO: 221 TRAV37*01 cacagtgcccacagtcacctgcacccggtacctaaagcttgctgaggggcctgggcacac ctccttttataagggccctggggcactgactataactctgctgcatacaaagggaaatat SEQ ID NO: 222 TRAV11*01 agtagtgtctccccagcacctgcagcctgtaccataacctgcagccgggacccttgacac aggctagccttgcaggtgggagtgaagattttttttttttttttgtatagagggaacttt SEQ ID NO: 223 TRAV15*01 cacagggtccccaagcacctgcagcctgtaccacaacctgcatccgggacccttgacaca gccttgccttgcaggtgggagtgaaggtgttgtctttatatgtagagagaacttctttat SEQ ID NO: 224 TRAV17*01 cacagtgttccccaggaacctgcagcctctacgcaaaccctgccaaagcagcttcttaga agccctaatagtgggtagaattagtggttatgtctttcagtcaagaagagtctacaaaca SEQ ID NO: 225 TRAV10*01 cactgtgctccacaggcacttgaagccagtatgcaaacctgcacctggaggttatcaagg aggcataggagttagagtagaccgttattttttatgcagaatatgatttcactagtgaat SEQ ID NO: 226 TRBV7-1*01 cacagcactactgctccagtgtcagcttggttccctaggaaatggggtttctagaacctg aatgctgacaaataagagttgtatatgtgtataccatgcaacctgcgtttaaaaatgtat SEQ ID NO: 227 TRAV24*01 cacagtgctgttcaggcacctgcagcccatacgcaaacctgtgtctggtgttgcactgtt accagcattgacaaagaaccatgagtaggatggaaaagacaagttcgttgaattacagtt SEQ ID NO: 228 TRAV39*01 cacagtgctcccctgacgccaccagtctgtacccaaacctgcagctggtgggcccactcc tcctgcaggaactatgactgtgaggcttcgttcactgtctgtacatttctttctgcaagg SEQ ID NO: 229 TRAV35*01 cacagtgctccccaaacacctgcagcctgtactcaaacttgcagctggaactctagtctc tatgctgccttcagctcttagtcctcttggcatgaaatgtgattatgcatgccacctttg SEQ ID NO: 230 TRAV12-2*01 cacagtgctccccagacacctgcagtctgtacccaaacctgccatgccccaggaatgcct gatgtagagcttagactgcagggtagtgaaactccccttgctctctagtttcaagtggaa SEQ ID NO: 231 TRAV29/DV5*01 cacagtgctctccaggcacctgcagcccgtactcaaacctgctttggggactcagactgg gagacacatagactcgcttccatttacacatgccaatatgagagattatgctttgaagta SEQ ID NO: 232 TRAV23/DV6*01 cacagtgctccccaggcacctgaagcctgtacccaaacctgcagttgaggttccagccaa accccacagtgggagcttacgtaggcagagatgtagcctagttttcatctgcatatgcaa SEQ ID NO: 233 TRAV28*01 cactgtgctcttcagacacctgcagcctatacatgaaaccatagctgaaggcctaaccca tccccgagagtggcagtaggtcccgatgtgattagcattgcattcccactgcctacatct SEQ ID NO: 234 TRAV25*01 cacagtgctccccaagcacctgctgcctgtctccaaatcttgccctgggtcttcaggagc agatcatcctactctccccaaagagcgggcgccagagaaagccaaagtcacaatgtctgt SEQ ID NO: 235 TRAV32*01 cacagaactcttcaggcacctgcaacctgtactcaaacctgcaactgggagtccagtcac attctttgtctttgaacgggttttgggttagaatggtttaccataatgtgcttgtttcta SEQ ID NO: 236 TRAV5*01 cacattgcttctcaggcacctgtaccctgtacccaaacctgcacctgggactaaagccac actctatttcctttacctttaagtcagggattttgctgtaaggtacttttaatgtacgga SEQ ID NO: 237 TRAV13-2*01 cacattgctttccaggcatctgtaaccatcacccaaacctgagatgggaggtgaagcagc atccctttcctttgcaataaattttagttatagcacttgtcattttgtttgttcataagt SEQ ID NO: 238 TRAV13-1*01 gcagcaagtacacattgcttcccaggcacctgctacccgtacacaaacctgagactggag ctgaagctgcaccccctttcctttgtcatagatcgtcaattatagcatttgtcatattgt 

1. A library of probes comprising the depletion probes in Table D or at least one of the V-gene and J-gene probes set forth in any of Tables 2.1, 4, B1, or B2.
 2. A method of capturing DNA fragments existing in a patient sample using a collection of nucleic acid hybrid capture probes, wherein each capture probe is designed to hybridize to a known V gene segment and/or a J gene segment within a B cell receptor and/or immunoglobulin genomic loci and comprises the probes of claim
 1. 3. The method of claim 2, further comprising sequencing the captured DNA fragments, wherein the sequencing can be used to determine clonotypes within the patient sample.
 4. The method of claim 3, wherein said sequencing is optimized for short read sequencing.
 5. The method of claim 3, further comprising amplifying a population of sequences using nucleic acid amplification probes/oligonucleotides that recognize the adapter prior to said sequencing. 6.-8. (canceled)
 9. The method of claim 2, wherein the patient sample comprises tissue, urine, cerebral spinal fluid, saliva, feces, ascities, pleural effusion, blood or blood plasma.
 10. The method of claim 2, wherein the patient sample comprises cell-free nucleic acids in blood plasma. 11.-19. (canceled)
 20. The method of claim 2, wherein the hybrid capture probes are immobilized on an array.
 21. The method of claim 2, wherein the hybrid capture probes comprise a label.
 22. The method of claim 21, wherein the label is used to distinguish between sequences bound to the screening probes and unbound double stranded fragments. 23.-26. (canceled)
 27. The method of claim 21, further comprising immunologically classifying a population of B-Cell receptor and/or immunoglobulin sequences by: (a) identifying all sequences containing a V gene segment from the sequences of the DNA fragments by aligning the sequences of the DNA fragments to a library of known V gene segment sequences; (b) trimming the identified sequences in (a) to remove any sequences corresponding to V gene segments to produce a collection of V-trimmed nucleotide sequences; (c) identifying all sequences containing a J gene segment in the population of V-trimmed nucleotide sequences by aligning the V-trimmed nucleotide sequences to a library of known J gene segment sequences; (d) trimming the V-trimmed nucleotide sequences identified in (c) to remove any sequences corresponding to J gene segments to produce VJ-trimmed nucleotide sequences; (e) identifying any D gene segment comprised in the VJ-trimmed nucleotide sequences identified in (d) by aligning the VJ-trimmed nucleotide sequences to a library of known D gene segment sequences; (f) for each VJ-trimmed nucleotides sequence identified in (d), assembling a nucleotide sequence comprising the V gene segment, any D gene segment, and the J gene segment identified in steps (a), (e) and (c) respectively; (g) selecting from the nucleotide sequence assembled in step (f) a junction nucleotide sequence comprising at least the junction between the V gene segment and the J gene segment, including any D gene segment, the junction nucleotide sequence comprising between 18 bp and 140 bp, preferably 40-100 bp, further preferably about 80 bp; and optionally (h) and (i): (h) translating each reading frame of the junction nucleotide sequence and its complementary strand to produce 6 translated sequences; and (i) comparing the 6 translated sequences to a library of known CDR3 regions of T-Cell receptor and/or immunoglobulin sequences to identify the CDR3 region in the DNA fragments.
 28. The method of claim 27, further comprising, prior to step (a), aligning left and right reads of overlapping initial DNA fragments to produce the DNA fragments on which step (a) is performed.
 29. The method of claim 27, wherein steps (a), (c), (e) are performed with BLASTn and step (i) is performed using expression pattern matching to known sequences and IMGT annotated data.
 30. The method of claim 21, further comprising identifying CDR3 regions in B-Cell receptor and/or immunoglobulin sequences by: (a) identifying a V gene segment comprised in the immunoglobulin sequence by aligning the immunoglobulin sequence to a library of known V gene segment sequences; (b) identifying a J gene segment comprised in the immunoglobulin sequence by aligning the immunoglobulin sequence to a library of known J gene segment sequences; (c) if V and J gene segments are identified, then comparing the immunoglobulin sequence to a library of known CDR3 regions of T-Cell receptor and/or immunoglobulin sequences to identify any CDR3 region in the immunoglobulin sequence.
 31. The method of claim 30, wherein steps (a) and (b) are performed using the Burrows-Wheeler Alignment or other sequence alignment algorithm.
 32. The method of claim 30, wherein if a CDR3 region is identified in step (c), then the method further comprises determining whether the identified V and J gene segments could be rearranged in the same locus using a heuristic approach. 33.-47. (canceled)
 48. The method of claim 30, further defined as a method for characterizing B-cell clonality as a feature of disease in the subject.
 49. The method of claim 48, wherein the subject has cancer.
 50. The method of claim 48, wherein the subject has a B-cell related disease, plasma cell disorder, preferably a B-cell lymphoma. 51.-53. (canceled) 